| Changes to trial information |
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Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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| 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 |
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Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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| 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. |
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Section Name
|
Field Name
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Date
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Reason
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Old Value
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Updated Value
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| Reporting |
IPD-Sharing time frame |
04/09/2020 |
Information not previously provided. |
|
This will be done within 12 months of the study completion date. |
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Section Name
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Field Name
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Date
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Reason
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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 |
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Section Name
|
Field Name
|
Date
|
Reason
|
Old Value
|
Updated Value
|
| Reporting |
IPD URL |
04/09/2020 |
Information not previously provided. |
|
Not available at present |
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Section Name
|
Field Name
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Date
|
Reason
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Old Value
|
Updated Value
|
| Reporting |
Study protocol document |
04/09/2020 |
Information not previously provided. |
|
Study Protocol, Clinical Study Report |
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Section Name
|
Field Name
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Date
|
Reason
|
Old Value
|
Updated Value
|
| Reporting |
Results Available |
04/09/2020 |
Information not previously provided. |
No |
No |
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Section Name
|
Field Name
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Date
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Reason
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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, |
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Section Name
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Field Name
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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 |
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Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
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| 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 |
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Section Name
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Field Name
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Date
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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
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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 |
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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 |
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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 |
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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 |
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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 |
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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, |