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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202106588702901 Date of Registration: 01/06/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Study of Monovalent and Bivalent Recombinant Protein Vaccines against COVID-19 in Adults 18 Years of Age and Older
Official scientific title A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older
Brief summary describing the background and objectives of the trial This is a Phase 3 study (efficacy study) of two experimental vaccines against SARS-CoV-2. The full names are: 1. Monovalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (CoV2 preS dTMAS03 [D614]) 2. Bivalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (CoV2 preS dTM-AS03 [D614 + B.1.351]) • This study is also known as “VAT00008” or “CoVPN 3005.” • The study vaccine is developed by Sanofi Pasteur, a company that produces vaccines against other diseases such as diphtheria, tetanus, pertussis, meningitis and influenza. • The vaccine will be manufactured using the same technology as is used to make an influenza vaccine that is licensed in the US for the prevention of influenza in adults, marketed as Flublok®. • The study will enroll about 21 046 participants globally. • The purpose of the study is to learn if: • The study vaccines can prevent symptomatic COVID-19 illness • The vaccines are safe • The vaccines make people too uncomfortable • The study vaccines can prevent infection with SARS-CoV-2 • The study vaccines can prevent severe COVID-19 illness and hospitalization
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VAT00008
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied covid 19 disease
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 30/06/2021
Actual trial start date 26/05/2021
Anticipated date of last follow up 30/09/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 21046
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
Control Group PLACEBO NA Approximately 365 days post-last injection (ie,approximately 386 days total) 2 injections seperated by 21 days 8000 Placebo
Experimental Group Vaccine CoV2 preS dTM-AS03 (D614) Each 0.5 mL dose of Study Intervention will contain the following 10 μg of preS-delta TM D614: prefusion S delta TM D614 COVID-19 antigen 2 injections / 21days apart Follow up Approximately 365 days post-last injection (ie, approximately 386 days total) two vaccine doses seperated by 21 days 5080
Experimental Group Vaccine CoV2 preS dTM-AS03 (D614 + B.1.351) Each 0.5 mL dose of Study Intervention will contain the following: preS-delta TM D614: prefusion S delta TM D614 COVID19 antigen, (5 μg) preS-delta TM B.1.351: prefusion S delta TM B.1.351 COVID19 antigen, (5 μg) 2 injections / 21days apart Follow up Approximately 365 days after last injection two vaccine doses seperated by 21 days 5443
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age I01: Aged 18 years or older on the day of inclusion Type of participant and disease characteristics I02: For persons living with HIV, stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3 I03: SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies I04: Does not intend to receive an authorized/approved COVID-19 vaccine despite encouragement by the Investigator to receive the authorized vaccine available to them at the time of enrollmenta Sex, contraceptive/barrier method and pregnancy testing requirements I05: A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile. OR • Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first study intervention administration until at least 12 weeks after the second study intervention administration. A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 25 hours before any dose of study intervention. Informed Consent I06: Informed consent form has been signed and dated Other Inclusions I07: Able to attend all visits and to comply with all study procedures I08: Covered by health insurance, only if required by local, regional or national regulations E01: Known systemic hypersensitivity to any of the vaccine components, or history of a lifethreatening reaction to a vaccine containing any of the same substancesa E02: Dementia or any other cognitive condition at a stage that could interfere with following the study procedures based on Investigator’s judgment E03: Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator’s judgment E04: Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator’s judgment E05: Unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the study procedures E06: Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided E07: Receipt of any vaccine in the 30 days preceding or on the day of the first study vaccination or planned receipt of any vaccine between the first study vaccination and in the 30 days following the second study vaccination except for influenza vaccination, which may be received at any time in relation to study intervention. E08: Prior administration of a coronavirus vaccine (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], SARS-CoV, Middle East Respiratory Syndrome [MERSCoV]) E09: Receipt of solid-organ or bone marrow transplants in the past 180 days E10: Receipt of anti-cancer chemotherapy in the last 90 days E11: Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure E12: Deprived of freedom by a 80 and over: 80+ Year,Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 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 18/07/2021 GHS ERC
Ethics Committee Address
Street address City Postal code Country
Research and Development Division Ghana Health Service P. O. Box MB190 ACCRA MB190 Ghana
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 10/08/2021 uncst
Ethics Committee Address
Street address City Postal code Country
Plot 6, Kimera Road, Ntinda kampala 6884 Uganda
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 10/08/2021 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200, NAIROBI, Kenya nairobi 54840-002 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Efficacy To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection Occurrences of symptomatic COVID-19 . safety To assess the safety of the CoV2 preS dTM-AS03 vaccines compared to placebo throughout the study.For participants in the Reactogenicity Subset: • Presence of solicited (pre-listed in the participant’s diary card / electronic diary card [DC/eDC] and [electronic] Case Report Form [CRF]) injection site reactions and systemic reactions occurring up to 7 days after each vaccination • Presence of non-serious unsolicited adverse events (AEs) reported up to 21 days after the last vaccination For all participants in the study: • Presence of unsolicited injection site and systemic AEs reported in the 30 minutes after each vaccination • Presence of medically-attended adverse events (MAAEs) throughout the study • Presence of serious adverse events (SAEs) throughout the study • Presence of adverse events of special interest (AESIs) throughout the study • Presence of virologically-confirmed SARSCoV-2 infections and/or symptomatic COVID- 19 365 days after second injections
Secondary Outcome 1) To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring ≥ 14 days after the second injection: • Prevention of SARS-CoV-2 infection and • Prevention of severe COVID-19 /Endpoints for secondary efficacy objective #1: • Occurrences of SARS-CoV-2 infection and • Occurrence of severe COVID-19 2) To assess, in participants who are SARS-CoV-2 naïve,the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the first injection /Endpoint for secondary efficacy objective #2: • Occurrences of symptomatic COVID-19/3) To assess, in all participants regardless of prior SARSCoV- 2 infection, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for:• Prevention of symptomatic COVID-19 and • Prevention of severe COVID-19 /4) To assess, in participants who are SARS-CoV-2 nonnaïve, the clinical efficacy of the CoV2 preS dTMAS03 vaccines for: • Prevention of symptomatic COVID-19 and • Prevention of severe COVID-19//Endpoints for secondary efficacy objective #3 and 4 Occurrences of symptomatic COVID-19 and Occurrence of severe COVID-19/5) To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of asymptomatic SARSCoV-2 infection./Endpoint for secondary efficacy objective #5:• Occurrences of asymptomatic SARS-CoV-2 infection/6) To assess the impact of the CoV2 preS dTM-AS03 vaccines in the reduction of viral burden and shedding among participants with symptomatic COVID-19 Endpoints for secondary efficacy objective #6:• Viral copies/mL in respiratory samples collected at each follow-up timepoint • Number of days with positive NAAT • Occurrences of positive NAAT in respiratory samples at each follow-up timepoint during symptomatic COVID-19 365 days after second injection
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kintampo Health Research Centre P. O. Box 200 Kintampo, Ghana Kintampo North Municipality Bono East Region kitampo Ghana
Navrongo Health Research Centre PO Box 114 Navrongo, Ghana navrongo Ghana
Kwame Nkrumah University of Science and Technology P.O. Box 1934 Kumasi kumasi Ghana
Moi University Clinical Research Centre Nandi Road, P.O. Box 4606 Eldoret, Rift Valley Eldoret 30100 Kenya
Walter Reed Project Research Center Hospital Road, PO Box 1357, Kericho, Rift Valley Kericho 20200 Kenya
Kombewa Clinical Research Center Off Kisumu-Bondo Road, Opposite Kombewa County Hospital P. O. Box 54 Kisumu 40100 Kenya
Ganjoni Clinic University of Washington/University of Nairobi Mombasa Kenya
Institute of Clinical Research University of Nairobi Kenyatta National Hospital P.O Box 19676 Nairobi 00202 Kenya
Kenya Medical Research Institute K N H, Mbagathi Rd nairobi Kenya
agha khan hospital 3rd Parklands Avenue nairobi Kenya
Walter Reed Prgramt Nigeria Clinical Research Centre 7 Usama Street, Maitama abuja Nigeria
HIV Vaccine Program LTD CRS Plot 51-59 Nakiwogo Road , P.O. Box 49 Entebbe Uganda
Makarere University Walter Reed Project Plot 42 Nakasero Rd Kampala Uganda
Jaramogi Oginga Odinga Teaching and Referral Hospital JOOTRH, Off Kakamega Road, P.O. Box 1578, 40100 Kisumu, Kenya Kisumu 40100 Kenya
KEMRI CCR Partners in Health RandD PHRD P.O. Box 54840 00200, Off Mbagathi Road, Nairobi, Kenya Nairobi 54840 Kenya
KEMRI CCR Butere County Hospital Site Kakamega KE, Unnamed Road, Butere, Kenya Butere Kenya
Kenya Medical Research Institute Kemri CMR Kisumu Kisumu Kenya
Baylor Uganda CRS Baylor college of Medicine Childrens foundation P.O.Box 72052, Clock Tower, Hospital Kampala Kampala 72052 Uganda
Medical Research Council Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit Research UnitP.O. Box 49 EntebbePlot 51-59 Nakiwogo Road, Entebbe Entebbe Uganda
Joint Clinical Research Centre JCRC Plot 101 Lubowa Estates Off Entebbe Road P.O. Box 10005, Kampala Uganda Kampala Uganda
Rakai Health Sciences Program Makerere University School of Public Health P.O. Box 7072, Kampala, Uganda Kampala 7072 Uganda
MU JHU Research Collaboration MUJHU CARE LTD CRS Upper Mulago Hill Road P.O BOX 23491, Kampala Kampala Uganda
Strengthening Institutional Capacity for Research Administration SICRA at Lira Regional Referral Hospital Plot 9/19, 21-41 Ngetta Road Police Rd, Lira P.O.BOX 2, LIRA Lira Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
ATI Advanced Technology International 315 Sigma Drive Summerville 29486 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor sanofi Pasteur Discovery Drive PA 18370-0187 Swiftwater 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 Kwaku Poku Asante kwakupoku.asante@kintampo-hrc.org +233208956598 Kintampo Health Research Centre P. O. Box 200
City Postal code Country Position/Affiliation
Kintampo North Municipality Bono East Region Ghana National coordinator for Ghana
Role Name Email Phone Street address
Public Enquiries hella ghrobel hella.ghorbel@mct-cro.com 21628881436 rue de la livre sterling
City Postal code Country Position/Affiliation
tunis Tunisia regulatory officer
Role Name Email Phone Street address
Scientific Enquiries gustavo Dyan gustavo.dayan@sanofi.com 15709727826 1 Discovery Drive
City Postal code Country Position/Affiliation
swiftwater 18370 United States of America scientific advisor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data dictionaries and all collected IPD will be stripped of identifiers and may be made available upon request. Informed Consent Form,Statistical Analysis Plan,Study Protocol upon request na
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