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: pactr.samrc.ac.za
Trial no.: PACTR202310615330649 Date of Approval: 20/10/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Sisonke 4 (SHERPA)/ mRNA-1273-P508
Official scientific title Open-label, phase 3 study to evaluate the effectiveness of heterologous mRNA-1273 boosting of the single or two dose Ad26.COV2.SCOVID-19 vaccine among health care workers in South Africa
Brief summary describing the background and objectives of the trial South Africa is severely affected by the global COVID-19 pandemic. As part of the Sisonke study, HCWs received a single dose of Ad26.COV2.S vaccine between 17 February and 17 May 2021, and were then offered a second dose between 8 November and 17 December 2021. Immunogenicity studies have since indicated that a heterologous mRNA vaccine boost strategy may elicit stronger neutralizing antibody responses among people who received the Ad26.COV2.S and other vector-based vaccines. The purpose of the study is therefore to evaluate the effectiveness of the heterologous mRNA-1273 (Moderna) boost against COVID-19 infections and severe disease (including deaths) among health care workers (HCWs) who participated in the Sisonke trial and received either a single dose or two doses of Ad26.COV2.S (Janssen, Johnson and Johnson) COVID-19 vaccine as their primary vaccination. Furthermore, the study aims to collect additional safety and immunogenicity data on the heterologous mRNA-1273 boost among Sisonke participants.
Type of trial CCT
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 SARS-CoV2
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 15/04/2022
Actual trial start date 24/05/2022
Anticipated date of last follow up 17/05/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 15000
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL N/A
Secondary Ids Issuing authority/Trial register
20210463 SAHPRA
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
Single Group Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group mRNA1273 vaccine 50 mcg in 0.25 mL Once A booster dose of 50 mcg in 0.25 mL will be administered IM at ≥3 months after the last Ad26.COV2.S dose. 15000
Control Group Not Applicable Not applicable Single arm study 100 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion criteria • Age 18 and older at time of enrolment • Sisonke participant • Received a priming Ad26.CoV2.S vaccination as part of the Sisonke study • If received a second dose of Ad26.CoV2.S vaccine as part of the Sisonke 2 study, this was administered at least 3 months ago • Participants who are pregnant or report breastfeeding at the time of enrolment may be included. • Willingness and ability to comply with vaccination plan and other study procedures. • Capable and willing to provide informed consent Exclusion criteria • Participants who have received any COVID-19 vaccines other than one or two doses of Ad26.CoV2.S through other means (for example, another mRNA booster dose). • Current participation in any other research studies (other than Sisonke) that would interfere with the objectives of this study. The determination of whether participation in another study would be exclusionary for a given participant will be made by the PI/designee. • Occurrence of a known COVID-19 outcome within 14 days of enrollment • Participants with a history of heparin-induced thrombocytopenia, or thrombosis and thrombocytopenia syndrome (TTS). • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of mRNA-1273. • Pregnancy which began prior to or within 30 days after the receipt of dose 2 of Ad26.COV2 and ongoing at the time of enrolment in this trial. • Acute infection (e.g. febrile illness) unless resolved before enrolment. • Any significant acute or chronic medical condition, situation or circumstance that in the opinion of the PI/designee makes the participant unsuitable for participation in the study, or jeopardises the safety or rights of the participant The following participants should only be enrolled after discussion with the PSRT: • Participants who are thought to have suffered a neurological or cardiac AE considered related to the Ad26.CoV2.S vaccine. • Participants reporting a non-infective SAE within the first 28 days following the first or second dose of Ad26.CoV2.S vaccine in the Sisonke 3B trial • History of myocarditis or pericarditis especially in young male • Chronic history of severe clotting disorders • Participants who suffered a thromboembolic AE following the Janssen Covid-19 vaccine. In the event of a clinical contraindication to receiving a heterologous mRNA-1273 booster, the study PSRT, comprising of medical experts in haematology, allergology and neurology supported by sa Adult: 19 Year-44 Year 18 Year(s) 105 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 20/04/2022 South African Health Products Regulatory Authority
Ethics Committee Address
Street address City Postal code Country
Head Office Building A Loftus Park 402 Kirkness Street Arcadia Pretoria 0083 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 06/05/2022 Wits 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 11/05/2022 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road Lyttelton Manor Ext 3 Centurion Pretoria 0157 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 19/04/2022 SAMRC Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive Parowvallei Cape Town 7505 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 09/05/2022 Stellenbosch University Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Stellenbosch University Matieland Stellenbosch 7602 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 07/04/2022 Sefako Makgatho University Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Molotlegi Street GaRankuwa Pretoria 0204 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 15/07/2022 University of Cape Town Faculty of Health Sciences Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
E52 Room 46 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 06/06/2022 UKZN Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
UKZN Research Ethics Office Westville Campus Govan Mbeki Building Durban 4000 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary objectives • To compare the effectiveness of Ad26.COV2.S vaccine with a heterologous mRNA-1273 boost on severe COVID-19 (including hospitalizations and deaths) in Sisonke participants, with Sisonke populations not boosted with mRNA-1273. • To compare the effectiveness of Ad26.COV2.S vaccine with a heterologous mRNA-1273 boost on any COVID-19 cases, as compared with Sisonke populations not boosted with mRNA-1273. Secondary objectives • To compare the effectiveness of a single dose of Ad26.COV2.S vaccine with or without a heterologous mRNA-1273 boost on any COVID-19 infection, COVID-19 hospitalizations and deaths in Sisonke participants. • To compare the effectiveness of two doses of Ad26.COV2.S vaccine with or without a heterologous mRNA-1273 boost on any COVID-19 infection, COVID-19 hospitalizations and deaths in Sisonke participants. • To compare the effectiveness of a single dose versus two doses of Ad26.COV2.S vaccine with a heterologous mRNA-1273 boost on any COVID-19 infection, COVID-19 hospitalizations and deaths in Sisonke participants. • To monitor safety among participants, including in pregnant and breastfeeding women, receiving a heterologous mRNA-1273 boost either after a single dose or two doses of Ad26.COV2.S vaccine. • In a subset of participants (approximately N=200), measure the early (Day 29) and late (Month 6) humoral and cellular immune responses to heterologous mRNA-1273 boost either after a single dose or two doses of Ad26.COV2.S vaccine. • To monitor the genetic diversity of breakthrough SARS CoV-2 infections. 1 year
Secondary Outcome Secondary Objec To compare the effectiveness of a single dose of Ad26.COV2.S vaccine with against without a heterologous mRNA-1273 boost on any COVID-19 infection, severe COVID, hospitalizations and deaths in Sisonke participants. Rates of COVID-19 infections, hospitalizations and deaths among participants who received a single Ad26.COV2.S dose with or without a mRNA booster To compare the effectiveness of two doses of Ad26.COV2.S vaccine with against without a heterologous mRNA-1273 boost on any COVID-19 infection, severe COVID, hospitalizations and deaths in Sisonke participants. Rates of COVID-19 infections, hospitalizations and deaths among participants who received two doses of Ad26.COV2.S with or without a mRNA booster To compare the effectiveness of a single dose versus two doses of Ad26.COV2.S vaccine with a heterologous mRNA-1273 boost on any COVID-19 infection, severe COVID, hospitalizations and deaths in Sisonke participants. Rates of COVID-19 infections, hospitalizations and deaths among mRNA boosted Sisonke who received one versus two previous doses of Ad26.COV2.S To monitor safety among participants, including among pregnant and breastfeeding women, receiving a heterologous mRNA-1273 boost either after a single dose or two doses of Ad26.COV2.S vaccine. All SAEs and adverse events of special interest and birth outcomes will be collected and reported for 6 months after the mRNA-1273 booster vaccination and for up to 1 year among pregnant women. In a subset of participants (approximately N=200), measure the humoral and cellular immune responses to heterologous mRNA-1273 boost either after a single dose or two doses of Ad26.COV2.S vaccine. Neutralization titres early (Day 29) and late (Month 6) post-boost versus baseline using pseudovirus and/or live virus neutralization assays. T cell response magnitudes post-boost versus baseline using intracellular cytokine staining. To monitor the genetic diversity of breakthrough SARS CoV-2 infections Genetic diversi Surveillance for effectiveness may continue for up to 2 years post vaccination until 17 May 2024. Surveillance for safety will be for a minimum of 6 month after mRNA-1273 booster vaccination
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
The Aurum Institute Gavin J Churchyard Legacy Centre Klerksdorp Clinical Research Centre The Aurum Institute Gavin J Churchyard Legacy Centre Klerksdorp Clinical Research Centre 201 Jade Square Centre Cnr Margaretha Prinsloo and OR Tambo Drive Klerksdorp 2571 South Africa
The Aurum Institute Pretoria Clinical Research Centre U5 Enterprise Building The Innovation Hub 6 Mark Shuttleworth Street Pretoria 0087 South Africa
The Aurum Institute Tembisa Clinical Research Centre cnr Rec RTJ Namane and Flint Mazibuko Drive Hospital ViewTembisa Gauteng Johannesburg 1632 South Africa
The Aurum Institute Rustenburg Clinical Research Centre First Floor 50 Steen Street Cnr Pretorius Street Rustenburg North West Province Rustenburg 0299 South Africa
CAPRISA eThekwini Clinical Research Site No 3 Richards Road Warwick Avenue Berea Durban 4001 South Africa
CAPRISA Vulindlela Clinical Research Site Adjacent to Mafakatini Primary Healthcare Clinic Road P402 Ward 9 Msunduzi Municipality uMgungundlovu District KwaZulu-Natal Durban South Africa
Clinical HIV Research Unit CHRU Themba Lethu Clinic University of the Witwatersrand Helen Joseph Hospital Perth Road Westdene Johannesburg South Africa
DTHF Desmond Tutu Health Foundation Emavundleni Research Centre 14 Sonwabile Drive Old Crossroads Klipfontein, Cape Town 7750 South Africa
FAMCRU Family Clinical Research Unit Ward J8 Tygerberg Hospital Department of Paeditrics and Child Health Stellenbosch University Francie van Zijl Parow Valley Cape Town 7505 South Africa
Josha Research 28 East Burger Street Bloemfontein Bloemfontein 9300 South Africa
DTHF Desmond Tutu Health Foundation Masiphumelele Research Office Guinea Fowl Rd Sunnydale Fish Hoek Cape Town 7975 South Africa
Wits RHI Shandukani Research Centre 7 Esselen Street Hillbrow Johannesburg 2001 South Africa
Bothas Hill Clinical Research Site South African Medical Research Council HIV Prevention Research Unit No1 Zulu road Valley Trust Bothas Hill Kwa-Zulu Natal Durban 3660 South Africa
Chatsworth Research Clinical Research Site South African Medical Research Council HIV and Other Infectious Disease Research Unit RK Khan Circle Chatsworth KwaZulu Natal Durban 4030 South Africa
Tongaat Clinical Research Site South African Medical Research Council HIV and Other Infectious Diseases Research Unit 12 to 14 Tesco Drive Tongaat KwaZulu Natal Tongaat 4400 South Africa
MRC Verulam HIV Prevention Research Unit 31 to 33 Wick Street Verulam 4340 South Africa
MeCRU Medunsa Clinical Research Unit MeCRU Clinical Research Unit Sefako Makgatho Health Science University Medunsa Pretoria 0204 South Africa
Ndlovu Research Centre Plot 1140 Elandsdoorn Dennilton Limpopo Dennilton 0470 South Africa
Nelson Mandela Academic Clinical Research Unit NeMACRU Sir Henry Hospital 17 Hospital Road Mthatha Mthatha 5099 South Africa
PHRU Perinatal HIV Research Unit Kliptown PHRU SowetoKliptown New Nurses Home Ground Floor Chris Hani Baragwanath Academic Hospital Chris Hani Road Diepkloof Soweto Johannesburg 1809 South Africa
PHOENIX Pharma Pty Ltd 2 Eastbourne Road Mount Croix Port Elizabeth Port Elizabeth 6001 South Africa
Setshaba Research Centre 2088 Block H Soshanguve Pretoria 0152 South Africa
TASK Applied Science Central 1 De Lange Street Bellville Cape Town 7530 South Africa
TASK Eden 4 Victoria Street George Eastern Cape George 6529 South Africa
Ubuntu Clinical Research Lenasia 212 Rose Avenue Lenasia Gauteng Johannesburg 1827 South Africa
Ubuntu Clinical Research Krugersdorp 71 Pretoria Street Krugersdorp Gauteng Johannesburg 1739 South Africa
Qhakaza Mbokodo Research Clinic Ladysmith KwaZulu Natal Ladysmith South Africa
Synergy Biomed Research Institute East London SBRI Suite 3 Tudor Court 280 Oxford Street East London East London South Africa
Isipingo Clinical Research Site South African Medical Research Council 3 to 13 Police Station Road Isipingo Road Isipingo Rail Isipingo Durban Durban 4110 South Africa
MERCLINCO Pty Ltd Middelburg 184 Cowen Ntuli Street Middelburg Middelburg 1050 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Moderna Moderna Inc 200 Technology Square Cambridge, Massachusetts USA 02138 Cambridge Massachusetts 02138 United States of America
National Department of Health of South Africa Civitas Building Cnr Thabo Sehume and Struben Streets Pretoria 0001 Pretoria 0001 South Africa
South African Medical Research Council SAMRC Francie van Zijl Drive Parowvallei Tygerberg Cape Town 7505 South Africa Cape Town 7505 South Africa
South African National Treasury 2nd Floor 40 Church Square Old Reserve Bank Building Pretoria Pretoria 0002 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Moderna Inc Moderna Inc 200 Technology Square Cambridge Massachusetts USA 02138 Cambridge 02138 United States of America Commercial Sector/Industry
Secondary Sponsor South African Medical Research Council SAMRC Francie van Zijl Drive Parowvallei Cape Town Tygerberg South Africa 7505 Cape Town 7505 South Africa Other Collaborative Groups
COLLABORATORS
Name Street address City Postal code Country
Institute of Infectious Disease and Molecular Medicine Professor Wendy Burgers University of Cape Town Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine Department of Pathology Division of Virology Viral Immunology Unit Anzio Road Observatory 7925 South Africa Cape Town 7925 South Africa
National Institute of Communicable Diseases Professor Penny Moore University of the Witwatersrand National Institute for Communicable Diseases, a Division of the NHLS Centre for HIV and STIs HIV Virology Section 1 Modderfontein Road Sandringham Johannesburg 2131South Africa Johannesburg 2131 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nigel Garrett nigel.garrett@caprisa.org +27316550617 Centre for the AIDS Programme of Research in South Africa CAPRISA Nelson R Mandela School of Medicine UKZN Private Bag X7 Congella 4013 Durban, South Africa
City Postal code Country Position/Affiliation
Durban 4013 South Africa CoPrincipal Investigator
Role Name Email Phone Street address
Scientific Enquiries Ameena Goga Ameena.Goga@mrc.ac.za +27123398524 South African Medical Research Council SAMRC Francie van Zijl Drive Parowvallei 7505 Tygerberg Cape Town South Africa
City Postal code Country Position/Affiliation
Cape Town 7505 South Africa CoPrincipal Investigator
Role Name Email Phone Street address
Public Enquiries Kentse Khuto kkhuto@hcrisa.org.za +27826593740 Hutchinson Center Research Institute of South Africa Chris Hani Baragwanath Academic Hospital Soweto 2196 South Africa
City Postal code Country Position/Affiliation
Johannesburg 2196 South Africa Senior Site Liaison Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The results of the trial will be shared with trial participant in a manner clearly stipulated by the protocol team. The Study Report will also be made available in line with the country, international and sponsor regulations. Clinical Study Report,Study Protocol 3 years. The protocol will share the clinical study report and make it publicly available once it is compiled.
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