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.: PACTR202006922165132 Date of Approval: 23/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title COVID-19 vaccine (ChAdOx1 nCoV-19) trial in South African Adults with and without HIV-infection
Official scientific title COVID-19: An Adaptive Phase I/II Randomized Placebo-controlled Trial to Determine Safety, Immunogenicity and Efficacy of Non-replicating ChAdOx1 SARSCoV-2 Vaccine in South African Adults Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV.
Brief summary describing the background and objectives of the trial A Phase I/II, double-blinded, placebo-controlled, individually randomized trial to assess safety, immunogenicity and efficacy of the candidate Coronavirus disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults aged 18-65 years living with and without HIV in South Africa. The vaccine or placebo will be administered via an intramuscular injection into the deltoid muscle of the nondominant arm. A total of 2000 participants will be enrolled into the trial; 1950 HIV-uninfected and 50 people living with HIV. There will be 4 trial groups, group 1 (n=50; intensive safety & immunogenicity cohort, HIV negative), group 2a (n=250; safety, intense immunogenicity & efficacy), group 2b (n=1650; safety, immunogenicity & vaccine efficacy) and group 3 (n=50, intensive safety & immunogenicity cohort, HIV positive). Participants will be followed up for 12 months after enrollment.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ChAdOx1
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Coronavirus COVID-19
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 24/06/2020
Actual trial start date 24/06/2020
Anticipated date of last follow up 30/12/2021
Actual Last follow-up date 31/01/2022
Anticipated target sample size (number of participants) 2000
Actual target sample size (number of participants) 2125
Recruitment status Completed
Publication URL https://doi.org/10.1016/ S0140-6736(20)32661-1; doi: 10.1016/S2352-3018(21)00157-0.; doi: 10.1056/NEJMoa2102214
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes 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 ChAdOx1 nCoV19 5x10^10vp of ChAdOx1 nCoV-19, administered twice 28 days apart Two doses, 28 days apart Group 1- IP. Participants (HIV-negative) will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. 25
Control Group Normal saline 0.9 0.5ml twice, 28 days apart twice, 28 days apart Group 1- placebo. Participants (HIV-negative) will receive two doses of Normal saline (0.9%) in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period 25 Placebo
Experimental Group ChAdOx1 nCov19 one OR two doses of vaccine 28 days apart One or two doses, 28 days apart Group 2a-IP. Participants (HIV-negative) will receive ONE OR TWO doses of 5x10^10vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1- dose) or 9 (2 doses) routine visits over a 12 month period 125
Control Group Normal saline 0.9 One or two doses 28 days apart One or two doses, 28 days apart Group 2a- placebo Participants (HIV-negative) will receive ONE OR TWO doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period 125 Placebo
Experimental Group ChAdOx1 nCoV19 5x10^10vp of ChAdOx1 nCoV-19. One or two doses 28 days apart One or two doses 28 days apart Group 2b- IP Participants will receive ONE OR TWO doses of 5x10^10vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period. 825
Control Group Normal saline 0.9 0.5ml. One or two doses, 28 days apart One or two doses 28 days apart Group 2b- placebo Participants will receive ONE OR TWO doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1- dose) or 6 (2 doses) routine visits over a 12 month period 825 Placebo
Experimental Group ChAdOx1 nCoV19 5x10^10vp of ChAdOx1 nCoV-19. Two doses 28 days apart Two doses 28 days apart Group 3- IP Participants (HIV-positive) will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. 25
Control Group Normal saline 0.9 0.5ml twice, 28 days apart Two doses, 28 days apart Group 3- placebo Participants (HIV-positive) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. 25 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Healthy adults aged 18-65 years. Documented result of not being infected with HIV (including screening by a rapid HIV antibody test) within two weeks of randomization into the study for Group-1 and Group-2 participants only. Able and willing (in the Investigator’s opinion) to comply with all study requirements. Willing to allow investigators review available medical records, and review all medical and laboratory records if participant is admitted to hospital with respiratory tract infection suspected or confirmed to be COVID-19. For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening (within 14 days of randomization) or vaccination. For Group-3 only (i.e. HIV-infected), need to have been on anti-retroviral treatment for at least three months and HIV-1 viral load is <1,000 copies/ml within two weeks of randomization. Agreement to refrain from blood donation during the course of the study. Provide written informed consent. Planned receipt of any vaccine other (licensed or investigational) than the study intervention within 30 days before and after each study vaccination. • Use of any unproven registered and unregistered treatments for COVID-19. • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). • Administration of immunoglobulins and/ or any blood products within the three months preceding the planned administration of the vaccine candidate. • HBSAg positivity on the screening sample. • Grade 2 or higher level of abnormality for FBC, U&E or LFT based on DAIDS Grading Criteria (Version 2.1, July 2017) • History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 vaccine. • Any history of hereditary angioedema or idiopathic angioedema. • Any history of anaphylaxis in relation to vaccination. • Pregnancy, lactation or willingness/intention to become pregnant during the study. • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of serious psychiatric condition likely to affect participation in the study. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture. • Any other serious chronic illness requiring hospital specialist supervision. • Chronic respiratory diseases, including asthma • Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness • Seriously overweight (BMI ≥ 40 Kg/m2) • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. • Suspected or known injecting drug abuse in the 5 years preceding enrollment. • Any clinically significant abnormal finding on screening urinalysis. • Any other significant disease Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 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 21/05/2020 University of the Witwatersrand Human Research Ethics Committee Medical
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 05/06/2020 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Research Services, University Offices Wellington Square Oxford 1200 United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV Seven days, 28 days, up to 365 days
Primary Outcome To assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 Up to 364 days post vaccination
Secondary Outcome To assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults Up to day 364 post vaccination
Primary Outcome To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV in people living with HIV Up to 364 days post vaccination
Primary Outcome To assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV after one and two doses of vaccine Up to 364 days post vaccination
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRC Vaccines Infectious Diseases Analytics Research Unit Chris Hani Baragwanath Academic Hospital, Chris Hani Rd, Diepkloof, Soweto Johannesburg 2093 South Africa
Wits RHI Shandukani Research Centre 7 Esselen Street, 2nd Floor, Hillbrow Johannesburg 2001 South Africa
Setshaba Research Centre 2088 Block H, Soshanguve Tshwane 0152 South Africa
PHRU Kliptown Office 4, Walter Sisulu Square, Corner Union Avenue Klipspruit Valley Road Johannesburg 1811 South Africa
Lung Infection and Immunity Unit Groote Schuur hospital Cape Town 7925 South Africa
FAMCRU Tygerberg Hospital, Francie Van Zijl Dr Cape Town 7505 South Africa
Soweto Clinical Trials Centre SCTC 1900 Sycamore St, Dlamini Soweto Johannesburg 1818 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
South African Medical Research Committee Francie van Zijl Drive Parowvallei, Cape Town 7505 South Africa
Bill and Melinda Gates Foundation 440 5th Ave N Seattle 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Research Services, University Offices Wellington Square, OX1 2JD Oxford 1200 United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Andrew Pollard Centre for Clinical Vaccinology and Tropical Medicine University of Oxford, Churchill Hospital, Old Road, Headington, OX3 7LE Oxford 3700 United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Shabir Madhi shabir.madhi@wits.ac.za +27828706672 11th floor, Nurses res, Chris Hani Baragwanath Academic hospital, Soweto
City Postal code Country Position/Affiliation
Johannesburg 2093 South Africa Professor of Vaccinology
Role Name Email Phone Street address
Scientific Enquiries Clare Cutland clare.cutland@wits.ac.za +27828096032 Faculty of Health Sciences, York Rd, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2093 South Africa Scientific coordinator
Role Name Email Phone Street address
Public Enquiries Theranne van Vuren theranne.vanvuren@wits-vida.org +27794931128 11th floor, Nurses res, Chris Hani Baragwanath Academic Hospital
City Postal code Country Position/Affiliation
Soweto Johannesburg 2093 South Africa Executive personal assistant
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The data accumulated from this study will be made publically available, within one year of completion of the study to any investigators or BMGF nominated partners, who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to. Any transfer of data, will be governed, by the terms of the local Ethics Committee (HREC). Data sharing will be done on a collaborative basis, with the site PI (or his nominee) being included in any further interrogation of the data. The data will be provided in the format in which it has been entered at RMPRU with the necessary data dictionary. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 12 months Controlled access, collaborative. To address specific questions not directly addressed under study objectives. Application will be to South African data team
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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 23/06/2020 edit An Adaptive Phase I/II Randomized Placebo-controlled Trial to Determine Safety, Immunogenicity and Efficacy of Non-replicating ChAdOx1 SARSCoV- 2 Vaccine in South African Adults Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV COVID-19: An Adaptive Phase I/II Randomized Placebo-controlled Trial to Determine Safety, Immunogenicity and Efficacy of Non-replicating ChAdOx1 SARSCoV-2 Vaccine in South African Adults Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Other Infections and Infestation disease 23/06/2020 edit Coronavirus Coronavirus COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 07/07/2020 Enrollment initiated 24 Jun 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 07/07/2020 Enrollment initiated 24 June 2020 Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 30/05/2022 Actual last visit 31 Jan 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 30/05/2022 Actual number of participants recruited 2125
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 30/05/2022 Recruitment completed Recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Publication URL 30/05/2022 Publication of results https://doi.org/10.1016/ S0140-6736(20)32661-1; doi: 10.1016/S2352-3018(21)00157-0.; doi: 10.1056/NEJMoa2102214
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 30/05/2022 7th site Soweto Clinical Trials Centre SCTC, 1900 Sycamore St, Dlamini, Soweto Johannesburg, 1818, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 30/05/2022 Updated e-mail address Principal Investigator, Shabir, Madhi, Prof., madhis@rmpru.co.za, , +27828706672, 11th floor, Nurses res, Chris Hani Baragwanath Academic hospital, Soweto, Johannesburg, 2093, South Africa, Professor of Vaccinology Principal Investigator, Shabir, Madhi, Prof., shabir.madhi@wits.ac.za, , +27828706672, 11th floor, Nurses res, Chris Hani Baragwanath Academic hospital, Soweto, Johannesburg, 2093, South Africa, Professor of Vaccinology
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 30/05/2022 Updated e-mail address Scientific Enquiries, Clare, Cutland, Dr., cutlandc@rmpru.co.za, , +27828096032, Faculty of Health Sciences, York Rd, Parktown, Johannesburg, 2093, South Africa, Scientific coordinator Scientific Enquiries, Clare, Cutland, Dr., clare.cutland@wits.ac.za, , +27828096032, Faculty of Health Sciences, York Rd, Parktown, Johannesburg, 2093, South Africa, Scientific coordinator
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 30/05/2022 Change in personnel Public Enquiries, Theranne, van Vuren, Mrs., theranne.vanvuren@wits-vida.org, , +27794931128, 11th floor, Nurses res, Chris Hani Baragwanath Academic Hospital, Soweto Johannesburg, 2093, South Africa, Executive personal assistant
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 30/05/2022 resignation Public Enquiries, Karishma, Naidoo, Mrs., naidook@rmpru.co.za, , +27725962836, RMPRU, 11th floor, nurses res, CHBAH, Johannesburg, 2093, South Africa, Research associate