Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202009726132275 Date of Approval: 14/09/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Study Looking at the Safety and Effectiveness of a COVID-19 Vaccine Plus Adjuvant in South African Adults
Official scientific title A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV. COVID-19
Brief summary describing the background and objectives of the trial This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. Amendment to extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination. To add an expansion of the ongoing Phase 2a/b, randomized, observer-blinded, placebo controlled 2019nCoV-501 trial that is to be conducted as an open-label, randomized study to evaluate the safety and immunogenicity of SARS CoV-2 rS with Matrix-M1 adjuvant in South African adult Health Care Workers.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 30/07/2020
Actual trial start date 20/08/2020
Anticipated date of last follow up 30/09/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 4704
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Cohort 1 HIV negative SARS-CoV-2 rS 5 μg 5 μg, administered by intramuscular injection on Day 0 and Day 21, ideally in alternating deltoids. Single injection Biological/Vaccine: SARS-CoV-2 rS 5 μg. Other Names: severe acute respiratory syndrome coronavirus 2 recombinant spike protein nanoparticle vaccine. Biological/Vaccine: Matrix-M1 50 μg, administered with SARS-CoV-2 rS. Other Names: Adjuvant. 2082
Control Group Cohort 1 HIV negative Placebo Administered by intramuscular injection on Day 0 and Day 21 Single Injection Placebo: Sodium chloride 0.9% (BP, sterile) 2082 Placebo
Experimental Group Cohort 2 HIV positive Biological/Vaccine: SARS-CoV-2 rS 5 μg, administered by intramuscular injection on Day 0 and Day 21 Single injection Biological/Vaccine: SARS-CoV-2 rS 5 μg. Other Names: severe acute respiratory syndrome coronavirus 2 recombinant spike protein nanoparticle vaccine. Biological/Vaccine: Matrix-M1 50 μg, administered with SARS-CoV-2 rS. Other Names: Adjuvant. 120
Control Group Cohort 2 HIV positive Placebo administered by intramuscular injection on Day 0 and Day 21 Single injection Sodium chloride 0.9% (BP, sterile) 120 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
All subjects: • Body mass index (BMI) of 17 to 40 kg/m². • Provides informed consent prior to study participation and is willing to comply with study procedures, including potential home visits. • Women of child-bearing potential must agree not to have sexual intercourse with men, or must consistently use an agreed method of contraception from at least 21 days prior to enrolment in the study, through 6 months after the last vaccination. HIV-negative subjects only: Documentation of HIV-negative test result by a method approved in South Africa. • Healthy at study screening, as determined by the investigator. HIV-positive subjects only: • Documentation of HIV-positive test result by a method approved in South Africa. • Receiving highly active antiretroviral therapy (HAART) and has been using the same regimen for at least 8 weeks before screening. Changes in antiretroviral dosage within 8 weeks of entering the study are allowed, as are exchanges in pharmacological formulations. • Medically stable at screening, as determined by the investigator. • Have a HIV-1 viral load < 1000 copies/mL within 45 days of randomization in the stud • Any current acute illness requiring medical or surgical care, or chronic illness (excluding HIV in HIV-positive subjects) that requires changes in medication in the past 2 months indicating that chronic illness/disease is not stable. • Chronic disease, including: a. hypertension (elevated blood pressure [BP]) ≥ grade 2 (systolic BP ≥ 160 mmHg; and/or diastolic BP ≥ 100 mmHg) according to the South African Hypertension Society’s Practice Guidelines; b. congestive heart failure with a history of an acute exacerbation of any severity in the prior 2 years; c. chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the past 2 years. Stable coronary heart disease is NOT exclusionary; d. evidence of unstable coronary artery disease in the past 3 months, as determined by the investigator; e. asthma requiring regular/chronic control medication; f. Type 1 and 2 diabetes (adult onset) requiring treatment with insulin; g. chronic kidney disease/renal insufficiency; h. Chronic gastrointestinal and hepatic diseases; i. chronic neurological diseases (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, epilepsy, or a history of stroke or previous neurological disorder within the past 12 months with residual symptoms). Subjects with a history of migraine or chronic headaches, or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded. • Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. • Prior receipt of investigational or approved COVID-19 vaccine at any time. • History of a diagnosis of suspected or confirmed COVID-19. • Received influenza (flu) vaccination within 14 days prior to first study vaccination; or any other vaccine within 4 weeks prior to first study vaccination; or planned vaccination with 5 weeks after first st 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 85 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/08/2020 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown, Johannesburg Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/10/2020 University of Cape Town Faculty of Health Sciences Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Groote Schuur Hospital Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/09/2020 University of Cape Town Faculty of Health Sciences Human Research ethics Committee
Ethics Committee Address
Street address City Postal code Country
Groote Schuur Hospital Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/10/2020 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/11/2020 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown, Johannesburg Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 02/03/2021 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/02/2021 University of Cape Town Human Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Old Main Building Groote Schuur Hospital Observatory Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/06/2021 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown Johannesburg 2193 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, analyzed overall, with a lower bound confidence interval (CI) of > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points. Except as otherwise specified, Cohort 1 (HIV-negative subjects) and Cohort 2 (HIV-positive subjects) will be analyzed overall and as separate populations. Day 28 to Day 386
Primary Outcome Numbers and percentages (with 95% CIs) of healthy HIV-negative and medically stable HIV-positive adult subjects, with solicited AEs (local, systemic) for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus. Day 7 and 28
Primary Outcome Numbers and percentages (with 95% CI) of subjects with unsolicited AEs (e.g, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 49 by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus. Day 0 to Day 49
Secondary Outcome Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, analysed separately, with a lower bound confidence interval (CI) of > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points. Day 28 until endpoint driven or at prespecified timepoints
Secondary Outcome Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 in serologically naïve (to SARS-CoV-2), healthy HIV-negative and medically stable HIV-positive adult subjects, with a lower bound CI > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint- driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points Day 28 until endpoint driven or at prespecified timepoints
Secondary Outcome Positive (+) PCR-confirmed SARS-CoV-2 illness with asymptomatic, symptomatic virologically confirmed, mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects from 7 days after the second vaccine dose (eg, Day 28). Day 28 to Day 386
Secondary Outcome (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe categories of COVID-19 as previously described. From Day 28
Secondary Outcome (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, requiring hospitalization (regardless of severity). From day 28
Secondary Outcome Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, overall and by age strata. Should COVID-19 illness scoring be substantially validated at the time of study start, application of the standard scoring may be applied. From Day 0
Secondary Outcome Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA using geometric mean titers (GMT) OR seroconversion rate (SCR) at Day 21 (post first dose), Day 35 (post second dose), and across later study time points in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2). Derived/calculated endpoints based on these data will include geometric mean ELISA units (GMEUs), geometric mean fold rise (GMFR), and SCR. Day 21, Day 35 and across later study time points
Secondary Outcome Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen as detected by ELISA, described across study time points with derived/calculated endpoints to include GMEUs, GMFR, and SCR in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2). Across study time points
Secondary Outcome Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding domain measured by serum titers in an ACE2 receptor binding inhibition assay, described across study time points, to include GMT, GMFR, SCR, and seroresponse rate (SRR) in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2. SRR is defined as the proportion of subjects with rises in titers exceeding the 95th percentile of placebo subjects at the same time point and based on prior SARS-CoV-2 exposure. Across study time points
Secondary Outcome Neutralizing antibody activity at Day 35 and across later study time points relative to baseline in healthy HIV-negative and medically stable HIV-positive adult subjects combined, by absolute titers and change from baseline, including SCR (≥ 4-fold change) and SRR, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2) to investigate whether baseline status (+/-) impacts response. Day 35 and across later study time points
Secondary Outcome Numbers and percentages (with 95% CI) of subjects with MAAEs, AESI, or SAE through the EOS by MedDRA classification, severity score, and relatedness in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus. Across study time points
Secondary Outcome As described in the primary and key secondary efficacy endpoints, combined and separately, and following the first or second dose, and by age strata. Day 7 and Day 28 and across study time points
Secondary Outcome One or more non-vaccine SARS-CoV-2 viral antigen-specific immune responses (eg, anti-N antibodies) measured by serum titers/units in an appropriate assay to indicate an interval seroconversion at a given post-vaccination study time point. Descriptive measures will include GMT, GMFR, SCR, and SRR. SRR is defined as the proportion of subjects with rises in antibody units/titers exceeding the 95th percentile of placebo subjects at the same time point and based on prior baseline exposure. Post-vaccination study time point
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Respiratory and Meningeal Pathogens Research Unit RMPRU Chris Hani Baragwanath Academic Hospital, Chris Hani Road, Soweto Johannesburg 2013 South Africa
Setshaba Research Centre 2088 Block H Soshanguve 0152 South Africa
Wits RHI Shandukani Research Centre Hillbrow Health Precinct Klein Street Johannesburg 2001 South Africa
University of Cape Town Lung Institute and Centre for Lung Infection and Immunity George Street Observatory Cape Town 7700 South Africa
Soweto Clinical Trials Centre Sycamore Street Soweto Johannesburg 1818 South Africa
South African Tuberculosis Vaccine Initiative Brewelskloof Hospital Haarlem Street Worcester 6850 South Africa
Josha Research 28 East Burger Street Bloemfontein 9300 South Africa
Umlazi Clinical Research Site Mangosuthu Highway Umlazi 4066 South Africa
Verulam Clinical Research Site South African Medical Research Council HIV Prevention Research Unit 31-33 Wick Street Verulam 4340 South Africa
KwaPhila Health Solution 26 Charles Strachan Road Durban 4091 South Africa
Durban International Clinical Research Site Enhancing Care Foundation Umbilo Road Durban 4013 South Africa
The Aurum Institute Pretoria Clinical Research Centre 6 Mark Shuttleworth Street Pretoria 0087 South Africa
Madibeng Centre for Research 40 Pienaar Street Brits South Africa
Limpopo Clinical Research Initiative 11 Van der Bijl street Thabazimbi 0380 South Africa
Peermed CTC Merk Kempton Cnr Voortrekker and Monument Rd Kempton Park 1619 South Africa
Mzansi Ethical Research Centre 184 Cowen Ntuli street Middelburg 1055 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 440 5th Ave N Seattle WA 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novavax Inc 21 Firstfield Road Gaithersburg MD 20878 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Shabir Madhi madhis@rmpru.co.za +27119899891 Chris Hani Baragwanath Academic Hospital Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 2013 South Africa Respiratory and Meningeal Pathogens Research Unit and MRC Vaccines and Infectious Diseases Analytics Research Unit
Role Name Email Phone Street address
Public Enquiries Gary Albert GAlbert@Novavax.com +12402684000 21 Firstfield Road
City Postal code Country Position/Affiliation
Gaithersburg MD 20878 United States of America Central Contact Person
Role Name Email Phone Street address
Scientific Enquiries Vivek Shinde vshinde@novavax.com +12402684000 21 Firstfield Road
City Postal code Country Position/Affiliation
Gaithersburg MD 20878 United States of America Study Chair
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes At a minimum, summary results or a link to summary results will be provided within the trial registration record. Clinical Study Report,Study Protocol This will be done within 12 months of the study completion date. Based on the data sharing agreement with the funder, which is in progress
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Not available at present No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 26/08/2020 Term COVID-19 added as per WHO request for ease of record identification A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV. COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 04/09/2020 Information not previously provided. At a minimum, summary results or a link to summary results will be provided within the trial registration record.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 04/09/2020 Information not previously provided. This will be done within 12 months of the study completion date.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 04/09/2020 Information not previously provided. Based on the data sharing agreement with the funder, which is in progress
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 04/09/2020 Information not previously provided. Not available at present
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 04/09/2020 Information not previously provided. Study Protocol, Clinical Study Report
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results Available 04/09/2020 Information not previously provided. No No
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 14/10/2020 Increase in the total sample size of the study from 2,904 to a minimum of approximately 3,200 to a maximum of approximately 4,404 subjects Experimental Group, Cohort 1 HIV negative, SARS-CoV-2 rS 5 μg 5 μg, administered by intramuscular injection on Day 0 and Day 21, ideally in alternating deltoids., Single injection, Biological/Vaccine: SARS-CoV-2 rS 5 μg. Other Names: severe acute respiratory syndrome coronavirus 2 recombinant spike protein nanoparticle vaccine. Biological/Vaccine: Matrix-M1 50 μg, administered with SARS-CoV-2 rS. Other Names: Adjuvant., 1332, Experimental Group, Cohort 1 HIV negative, SARS-CoV-2 rS 5 μg 5 μg, administered by intramuscular injection on Day 0 and Day 21, ideally in alternating deltoids., Single injection, Biological/Vaccine: SARS-CoV-2 rS 5 μg. Other Names: severe acute respiratory syndrome coronavirus 2 recombinant spike protein nanoparticle vaccine. Biological/Vaccine: Matrix-M1 50 μg, administered with SARS-CoV-2 rS. Other Names: Adjuvant., 2082,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 14/10/2020 Increase in the total sample size of the study from 2,904 to a minimum of approximately 3,200 to a maximum of approximately 4,404 subjects Control Group, Cohort 1 HIV negative, Placebo Administered by intramuscular injection on Day 0 and Day 21, Single Injection, Placebo: Sodium chloride 0.9% (BP, sterile) , 1332, Placebo Control Group, Cohort 1 HIV negative, Placebo Administered by intramuscular injection on Day 0 and Day 21, Single Injection, Placebo: Sodium chloride 0.9% (BP, sterile) , 2082, Placebo
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 14/10/2020 Increase in the upper limit of the eligible age to < 85 years in Cohort 1 only, with an effort to enroll a target of 10 25% of subjects ≥ 65 to <85 years of age. RATIONALE: older adults represent an important risk group to be prioritized in the early rollout of COVID-19 vaccine deployment globally because this population is at increased risk serious COVID-19 outcomes Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s) Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Maximum age 14/10/2020 Increase in the upper limit of the eligible age to < 85 years in Cohort 1 only, with an effort to enroll a target of 10 25% of subjects ≥ 65 to <85 years of age. RATIONALE: older adults represent an important risk group to be prioritized in the early rollout of COVID-19 vaccine deployment globally because this population is at increased risk serious COVID-19 outcomes 64 Year(s) 85 Year(s)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 14/10/2020 Exclusion Criteria (Section 4.2) were broadened or clarified as follows: o Broaden the eligibility criteria by providing the actual blood pressure values that define hypertension according to the South African Hypertension Society Practice Guidelines (Exclusion Criterion 2a). This exclusion criterion now references local South African Hypertension Society Guidelines and allow for mild Grade 1 hypertension. o Broaden the eligibility criteria by defining congestive heart failure (Exclusion Criterion 2b). Mild congestive heart failure without history of exacerbation in the prior 2 years is now allowed. o Clarify that stable coronary heart disease was not exclusionary (Exclusion Criterion 2d). o Broaden the eligibility criteria by defining asthma (Exclusion Criterion 2e). Mild, intermittent asthma not requiring chronic control medication is now allowed. o Add type 1 diabetes to the exclusion criteria since type 1 diabetes subjects require insulin and clarified that non-insulin dependent type 2 diabetes subjects were not exclusionary (Exclusion Criterion 2f). o Clarify chronic neurological diseases (Exclusion Criterion 2i). o Added that the use of inhaled glucocorticoids was permitted (Exclusion Criterion 8). • Any current acute illness requiring medical or surgical care, or chronic illness (excluding HIV in HIV-positive subjects) that requires changes in medication in the past 2 months indicating that chronic illness/disease is not stable. • Chronic disease, including: a. hypertension uncontrolled for age; b. congestive heart failure; c. chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the past 2 years; d. evidence of unstable coronary artery disease in the past 3 months, as determined by the investigator; e. asthma; f. Type 2 diabetes (adult onset) requiring treatment with insulin; g. chronic kidney disease/renal insufficiency; h. Chronic gastrointestinal and hepatic diseases; i. chronic neurological diseases (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, epilepsy, or a history of stroke or previous neurological disorder within the past 12 months with residual symptoms). Subjects with a history of migraine or chronic headaches, or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded. • Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. • Prior receipt of investigational or approved COVID-19 vaccine at any time. • History of a diagnosis of suspected or confirmed COVID-19. • Received influenza (flu) vaccination within 14 days prior to first study vaccination; or any other vaccine within 4 weeks prior to first study vaccination; or planned vaccination with 5 weeks after first study vaccination. • Any autoimmune or immunodeficiency disease/condition (excluding HIV in HIV-positive patients). • Chronic (more than 14 days continuous) administration of immunosuppressant, systemic glucocorticosteroids, or other immune modifying drug • Received immunoglobulin, blood-derived products, or other immunosuppressan • Any current acute illness requiring medical or surgical care, or chronic illness (excluding HIV in HIV-positive subjects) that requires changes in medication in the past 2 months indicating that chronic illness/disease is not stable. • Chronic disease, including: a. hypertension (elevated blood pressure [BP]) ≥ grade 2 (systolic BP ≥ 160 mmHg; and/or diastolic BP ≥ 100 mmHg) according to the South African Hypertension Society’s Practice Guidelines; b. congestive heart failure with a history of an acute exacerbation of any severity in the prior 2 years; c. chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbation of any severity in the past 2 years. Stable coronary heart disease is NOT exclusionary; d. evidence of unstable coronary artery disease in the past 3 months, as determined by the investigator; e. asthma requiring regular/chronic control medication; f. Type 1 and 2 diabetes (adult onset) requiring treatment with insulin; g. chronic kidney disease/renal insufficiency; h. Chronic gastrointestinal and hepatic diseases; i. chronic neurological diseases (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, epilepsy, or a history of stroke or previous neurological disorder within the past 12 months with residual symptoms). Subjects with a history of migraine or chronic headaches, or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded. • Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. • Prior receipt of investigational or approved COVID-19 vaccine at any time. • History of a diagnosis of suspected or confirmed COVID-19. • Received influenza (flu) vaccination within 14 days prior to first study vaccination; or any other vaccine within 4 weeks prior to first study vaccination; or planned vaccination with 5 weeks after first st
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To achieve increased subject numbers Josha Research, 28 East Burger Street, Bloemfontein, 9300, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To achieve recruitment of increased subject numbers Umlazi Clinical Research Site, Mangosuthu Highway, Umlazi, 4066, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To achieve recruitment of increased subject numbers Verulam Clinical Research Site South African Medical Research Council HIV Prevention Research Unit, 31-33 Wick Street, Verulam, 4340, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To achieve recruitment of increased subject numbers KwaPhila Health Solution, 26 Charles Strachan Road, Durban, 4091, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To enable recruitment of increased subject numbers Durban International Clinical Research Site Enhancing Care Foundation, Umbilo Road, Durban, 4013, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To enable recruitment of increased subject numbers The Aurum Institute Pretoria Clinical Research Centre, 6 Mark Shuttleworth Street, Pretoria, 0087, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To enable recruitment of increased subject numbers Madibeng Centre for Research, 40 Pienaar Street, Brits, , South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/10/2020 To enable recruitment of increased subject numbers Limpopo Clinical Research Initiative, 11 Van der Bijl street , Thabazimbi, 0380, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2020 Initial approval for UCT site TRUE, University of Cape Town Faculty of Health Sciences Human Research Ethics Committee , Groote Schuur Hospital, Cape Town, 7925, South Africa, , 01 Oct 2020, 0214066626, hrec-enquiries@uct.ac.za, 12319_12775_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2020 Initial approval for UCT site TRUE, University of Cape Town Faculty of Health Sciences Human Research ethics Committee, Groote Schuur Hospital, Cape Town, 7925, South Africa, , 28 Sep 2020, +27214066626, hrec-enquiries@uct.ac.za, 12319_12776_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 15/10/2020 Approval of Protocol amendment. Version 3.0/Amendment 2 dated 09 September 2020 TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace, Johannesburg, 2193, South Africa, , 05 Oct 2020, +27112749200, jennifer.palmer@witshealth.co.za, 12319_12778_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 01/12/2020 Increase in the total sample size of the study from 2,904 to a minimum of approximately 3,200 to a maximum of approximately 4404 subjects. All additional subjects will be added to Cohort 1 (HIV-negative subjects). RATIONALE: the increase in sample size will allow a more rapid accumulation of efficacy endpoints to help accelerate the timing of the endpoint-driven efficacy analysis (and in turn accelerate vaccine development), and to account for the declining intensity of the COVID-19 epidemic in South Africa. 2904 4040
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 01/12/2020 Additional investigator site to meet enrollment numbers The Aurum Institute Pretoria Clinical Research Centre, 6 Mark Shuttleworth Street, Pretoria, 0087, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 01/12/2020 Additional investigator site to meet enrollment numbers Peermed CTC Merk Kempton, Cnr Voortrekker and Monument Rd, Kempton Park, 1619, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 01/12/2020 Duplicate The Aurum Institute Pretoria Clinical Research Centre, 6 Mark Shuttleworth Street, Pretoria, 0087, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 01/12/2020 To meet target recruitment numbers Mzansi Ethical Research Centre, 184 Cowen Ntuli street, Middelburg, 1055, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 01/12/2020 Increase in the total sample size of the study from 2,904 to a minimum of approximately 3,200 to a maximum of approximately 4404 subjects. All additional subjects will be added to Cohort 1 (HIV-negative subjects). RATIONALE: the increase in sample size will allow a more rapid accumulation of efficacy endpoints to help accelerate the timing of the endpoint-driven efficacy analysis (and in turn accelerate vaccine development), and to account for the declining intensity of the COVID-19 epidemic in South Africa. 4040 4404
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 26/01/2021 Recruitment number reached Recruiting Closed to recruitment,follow-up continuing
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 Protocol Amendment 3 describes a single set of objectives and endpoints including a single primary efficacy endpoint for the overall population with the analysis of other endpoints conducted for the overall population and as well as separately for HIV-negative and HIV-positive subjects. The rationale for this approach is to allow study results to be more representative of, and generalizable to, the overall South African population in terms of makeup of the predominant risk groups; consequently, all endpoints will be analyzed both in the overall study population, as well as separately, by HIV-negative and HIV-positive cohorts. The choice of a single primary efficacy endpoint (rather than the 2 independent primary efficacy endpoints as indicated in previous amendments) of positive (+) polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness with symptomatic mild, moderate, or severe coronavirus disease 2019 (COVID-19), was to align and synchronize with the emerging consensus among vaccine developers and global regulators on the need to measure prevention of PCR-confirmed, symptomatic mild, moderate, or severe COVID-19 as the primary endpoint of COVID-19 in vaccine efficacy studies. Primary Outcome, Total number of HIV- participants with first COVID-19 infection and mild, moderate or severe symptoms COVID-19 confirmed by PCR. Symptoms include respiratory (new onset cough, new onset rapid breathing, new onset shortness of breath, sore throat, loss of smell, nasal congestion, runny nose) and non-respiratory (fever, myalgia, chills, loss of taste, headache, diarrhea, tiredness, nausea or vomiting, loss of appetite)., Day 28 Primary Outcome, Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, analyzed overall, with a lower bound confidence interval (CI) of > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points. Except as otherwise specified, Cohort 1 (HIV-negative subjects) and Cohort 2 (HIV-positive subjects) will be analyzed overall and as separate populations., Day 28 to Day 386
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 In line with Protocol Amendment 3 Primary Outcome, Total number of HIV- participants with first COVID-19 infection and mild or moderate symptoms COVID-19 confirmed by PCR. Symptoms include respiratory (new onset cough, new onset rapid breathing, new onset shortness of breath, sore throat, loss of smell, nasal congestion, runny nose) and non-respiratory (fever, myalgia, chills, loss of taste, headache, diarrhea, tiredness, nausea or vomiting, loss of appetite). Moderate symptoms are ≥1 of fever plus any 2 COVID-19 symptoms for ≥3 days, high fever for ≥3 days, any evidence of significant lower respiratory tract infection. Severe symptoms are ≥1 of tachypnea, resting heart rate ≥125 beats per minute, oxygen saturation ≤93% on room air or PAO#/FiO#, high flow oxygen therapy/non--invasive ventilation/non-invasive positive pressure ventilation, mechanical ventilation or extracorporeal membrane oxygenation, ≥1 major organ system dysfunction or failure, admission to an ICU, death. , Day 28 Primary Outcome, Numbers and percentages (with 95% CIs) of healthy HIV-negative and medically stable HIV-positive adult subjects, with solicited AEs (local, systemic) for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus. , Day 7 and 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Number of HIV- participants with solicited adverse events (AEs) following first vaccination, Day 0 to Day 7 Primary Outcome, Numbers and percentages (with 95% CI) of subjects with unsolicited AEs (e.g, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 49 by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus., Day 0 to Day 49
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Number of HIV+ participants with solicited adverse events (AEs) following first vaccination, Day 0 to Day 7
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Number of HIV- participants with solicited adverse events (AEs) following second vaccination, Day 21 to Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Number of HIV+ participants with solicited adverse events (AEs) following second vaccination, Day 21 to Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV+ participants, Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Percentage of HIV+ participants with unsolicited adverse events (AEs), Thru day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Number of HIV+ participants with unsolicited adverse events (AEs), Thru day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Percentage of HIV+ participants with solicited adverse events (AEs) following second vaccination, Day 21 to Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Percentage of HIV- participants with solicited adverse events (AEs) following second vaccination, 21 to Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Percentage of HIV+ participants with solicited adverse events (AEs) following first vaccination, Day 0 to Day 7
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Primary Outcome, Percentage of HIV- participants with solicited adverse events (AEs) following first vaccination, Day 0 to Day 7
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3: - Indicate that as a key secondary efficacy endpoint, evaluations of positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19, in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, will be analyzed separately. - Add as an additional secondary endpoint, positive (+) PCR-confirmed SARS-CoV-2 illness with asymptomatic, symptomatic virologically confirmed, mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects from 7 days after the second vaccine dose (eg, Day 28). - Indicate that exploratory endpoints will be evaluated as described for primary and key secondary efficacy endpoints and by age strata. Secondary Outcome, Total number of HIV- participants with first COVID-19 infection with any symptoms COVID-19 confirmed by PCR. Mild symptoms are ≥1 of fever, new onset cough, ≥2 COVID-19 respiratory/nonrespiratory symptoms, and does not meet criteria for moderate or severe symptoms. Moderate symptoms are ≥1 of fever plus any 2 COVID-19 symptoms for ≥3 days, high fever for ≥3 days, any evidence of significant lower respiratory tract infection. Severe symptoms are ≥1 of tachypnea, resting heart rate ≥125 beats per minute, oxygen saturation ≤93% on room air or PAO#/FiO#, high flow oxygen therapy/non--invasive ventilation/non-invasive positive pressure ventilation, mechanical ventilation or extracorporeal membrane oxygenation, ≥1 major organ system dysfunction or failure, admission to an ICU, death., Up to 12 months after last vaccination day 21 Secondary Outcome, Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, analysed separately, with a lower bound confidence interval (CI) of > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points., Day 28 until endpoint driven or at prespecified timepoints
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Percentage of HIV+ participants with MAAEs (Medically Attended Adverse Events), AESI (Adverse Events of Special Interest) or SAEs (Serious Adverse Events). Assessed by MedDRA classification, severity score and relatedness, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Percentage of HIV- participants with MAAEs (Medically Attended Adverse Events), AESI (Adverse Events of Special Interest) or SAEs (Serious Adverse Events). Assessed by MedDRA classification, severity score and relatedness, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Number of HIV+ participants with MAAEs, AESI or SAE. Assessed by MedDRA classification, severity score and relatedness, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Number of HIV- participants with MAAEs, AESI or SAE. Assessed by MedDRA classification, severity score and relatedness, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change in neutralizing antibody activity in HIV+ participants, Baseline and 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change in neutralizing antibody activity in HIV- participants, Baseline and 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change in neutralizing antibody activity in HIV+ participants at Day 35, Baseline and Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change in neutralizing antibody activity in HIV- participants at Day 35, Baseline and Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Epitope-specific immune responses to COVID-19 protein receptor binding domain in HIV+ participants. Measured by serum titers in an ACE2 receptor binding inhibition assay, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Epitope-specific immune responses to COVID-19 protein receptor binding domain in HIV- participants. Measured by serum titers in an ACE2 receptor binding inhibition assay, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change from baseline in serum IgG antibody levels specific for COVID-19 in HIV+ participants. Measured by ELISA, Baseline and 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change from baseline in serum IgG antibody levels specific for COVID-19 in HIV- participants. Measured by ELISA, Baseline and 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change from baseline in serum IgG antibody levels specific for COVID-19 in HIV+ participants at Day 35. Measured by ELISA, Baseline and Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Change from baseline in serum IgG antibody levels specific for COVID-19 in HIV- participants at Day 35. Measured by ELISA, Baseline and Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV+ participants. Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Up to 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV- participants. Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Up to 6 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV+ participants (post-second dose). Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV- participants (post-second dose). Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Day 35
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV+ participants (post-first dose). Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for COVID-19 in HIV- participants (post-first dose). Measured by ELISA using geometric mean titers (GMT) or seroconversion rate (SCR), Day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, COVID-19 symptom duration in HIV+ participants, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, COVID-19 symptom duration in HIV- participants, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Maximum severity score of COVID-19 infection in HIV+ participants. Should COVID-19 illness scoring be substantially validated at the time of study start, application of the standard scoring may be applied., Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Maximum severity score of COVID-19 infection in HIV- participants. Should COVID-19 illness scoring be substantially validated at the time of study start, application of the standard scoring may be applied., Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Incidence of virologically confirmed COVID-19 infection in HIV+ participants, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Incidence of virologically confirmed COVID-19 infection in HIV- participants, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Total number of HIV- participants with first COVID-19 infection requiring hospitalization, Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Total number of HIV+ participants with first COVID-19 infection with any symptoms COVID-19 confirmed by PCR. Mild symptoms are ≥1 of fever, new onset cough, ≥2 COVID-19 respiratory/nonrespiratory symptoms, and does not meet criteria for moderate or severe symptoms. Moderate symptoms are ≥1 of fever plus any 2 COVID-19 symptoms for ≥3 days, high fever for ≥3 days, any evidence of significant lower respiratory tract infection. Severe symptoms are ≥1 of tachypnea, resting heart rate ≥125 beats per minute, oxygen saturation ≤93% on room air or PAO#/FiO#, high flow oxygen therapy/non--invasive ventilation/non-invasive positive pressure ventilation, mechanical ventilation or extracorporeal membrane oxygenation, ≥1 major organ system dysfunction or failure, admission to an ICU, death., Up to 12 months after last vaccination day 21
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Positive (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 in serologically naïve (to SARS-CoV-2), healthy HIV-negative and medically stable HIV-positive adult subjects, with a lower bound CI > 0, from 7 days after the second vaccine dose (e.g, Day 28) until the endpoint- driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints across the 2 study vaccine arms and/or at prespecified time points , Day 28 until endpoint driven or at prespecified timepoints
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Positive (+) PCR-confirmed SARS-CoV-2 illness with asymptomatic, symptomatic virologically confirmed, mild, moderate, or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects from 7 days after the second vaccine dose (eg, Day 28). , Day 28 to Day 386
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe categories of COVID-19 as previously described., Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, requiring hospitalization (regardless of severity)., From day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe categories of COVID-19 as previously described., Day 28 Secondary Outcome, (+) PCR-confirmed SARS-CoV-2 with COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe categories of COVID-19 as previously described., From Day 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe COVID-19 in serologically naïve (to SARS-CoV-2) healthy HIV-negative and medically stable HIV-positive adult subjects, overall and by age strata. Should COVID-19 illness scoring be substantially validated at the time of study start, application of the standard scoring may be applied. , From Day 0
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA using geometric mean titers (GMT) OR seroconversion rate (SCR) at Day 21 (post first dose), Day 35 (post second dose), and across later study time points in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2). Derived/calculated endpoints based on these data will include geometric mean ELISA units (GMEUs), geometric mean fold rise (GMFR), and SCR. , Day 21, Day 35 and across later study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen as detected by ELISA, described across study time points with derived/calculated endpoints to include GMEUs, GMFR, and SCR in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2)., Across study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding domain measured by serum titers in an ACE2 receptor binding inhibition assay, described across study time points, to include GMT, GMFR, SCR, and seroresponse rate (SRR) in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2. SRR is defined as the proportion of subjects with rises in titers exceeding the 95th percentile of placebo subjects at the same time point and based on prior SARS-CoV-2 exposure. , Across study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Neutralizing antibody activity at Day 35 and across later study time points relative to baseline in healthy HIV-negative and medically stable HIV-positive adult subjects combined, by absolute titers and change from baseline, including SCR (≥ 4-fold change) and SRR, regardless of baseline serostatus and stratified by baseline serostatus (to SARS-CoV-2) to investigate whether baseline status (+/-) impacts response. , Day 35 and across later study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, Numbers and percentages (with 95% CI) of subjects with MAAEs, AESI, or SAE through the EOS by MedDRA classification, severity score, and relatedness in healthy HIV-negative and medically stable HIV-positive adult subjects, regardless of baseline serostatus and stratified by baseline serostatus. , Across study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, As described in the primary and key secondary efficacy endpoints, combined and separately, and following the first or second dose, and by age strata., Day 7 and Day 28 and across study time points
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 26/01/2021 As per Protocol Amendment 3 Secondary Outcome, One or more non-vaccine SARS-CoV-2 viral antigen-specific immune responses (eg, anti-N antibodies) measured by serum titers/units in an appropriate assay to indicate an interval seroconversion at a given post-vaccination study time point. Descriptive measures will include GMT, GMFR, SCR, and SRR. SRR is defined as the proportion of subjects with rises in antibody units/titers exceeding the 95th percentile of placebo subjects at the same time point and based on prior baseline exposure., Post-vaccination study time point
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/01/2021 Protocol Amendment 3 approval TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, Johannesburg, 2193, South Africa, , 30 Nov 2020, +27112749200, jennifer.palmer@witshealth.co.za,
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 20/07/2021 1. Design amended to cross-over afford benefit (as assessed by regulatory agencies) to all subjects. 2. A further amendment included a sub-study for Healthcare Worker vaccination. This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. Amendment to extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 20/07/2021 To provide for the vaccination of 300 Health Care Workers at participating sites 4404 4704
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 20/07/2021 1. Design amended to cross-over afford benefit (as assessed by regulatory agencies) to all subjects. 2. A further amendment included a sub-study for Healthcare Worker vaccination. This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. Amendment to extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 20/07/2021 To provide for the vaccination of 300 Health Care Workers at participating sites 4404 4704
Section Name Field Name Date Reason Old Value Updated Value
Study Design Intervention assignment 20/07/2021 extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Crossover: all participants receive all interventions in different sequence during study
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/07/2021 Change of study design to cross over study TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, 2193, South Africa, , 17 Feb 2021, 0027112749200, jennifer.palmer@witshealth.co.za, 12319_13396_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/07/2021 Change to cross - over study TRUE, University of Cape Town Human Ethics Committee, Old Main Building Groote Schuur Hospital Observatory, Cape Town, 7925, South Africa, , 24 Feb 2021, 00216501236, hrec-enquiries@uct.ac.za, 12319_13397_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/07/2021 Date of approval corrected TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, 2193, South Africa, , 17 Feb 2021, 0027112749200, jennifer.palmer@witshealth.co.za, 12319_13396_4737.pdf TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, 2193, South Africa, , 02 Mar 2021, 0027112749200, jennifer.palmer@witshealth.co.za, 12319_13396_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 20/07/2021 To vaccinate Health Care Workers at participating sites This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. Amendment to extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination. This is a study to evaluate the safety and effectiveness of a COVID-19 vaccine plus adjuvant in healthy HIV-negative and HIV-positive adults. A vaccine causes the body to have an Immune response that can help improve the body's reaction to reinfection by the virus, and reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the body's immune response to see if the adjuvant affects the body's immune response. Participants in the study will randomly be assigned to receive the SARS-CoV-2 rS vaccine plus adjuvant, or to receive placebo. Each participant in the study will receive a total of two intra-muscular injections over the course of the study. Amendment to extend the trial with a blinded crossover vaccination period during which subjects will receive either a booster injection of active vaccine or 2 injections of active vaccine 21 days apart, beginning 6 months after the initial vaccination. To add an expansion of the ongoing Phase 2a/b, randomized, observer-blinded, placebo controlled 2019nCoV-501 trial that is to be conducted as an open-label, randomized study to evaluate the safety and immunogenicity of SARS CoV-2 rS with Matrix-M1 adjuvant in South African adult Health Care Workers.
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/07/2021 Letter uploaded TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, Johannesburg, 2193, South Africa, , 30 Nov 2020, +27112749200, jennifer.palmer@witshealth.co.za, TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, Johannesburg, 2193, South Africa, , 30 Nov 2020, +27112749200, jennifer.palmer@witshealth.co.za, 12319_12979_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/07/2021 HCW approval letter uploaded TRUE, University of the Witwatersrand Human Research Ethics Committee, 31 Princess of Wales Terrace Parktown, Johannesburg, 2193, South Africa, , 14 Jun 2021, 0027112749200, jennifer.palmer@witshealth.co.za, 12319_13403_4737.pdf