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.: PACTR202011523101903 Date of Approval: 03/11/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Study of Recombinant Protein Vaccine with Adjuvant against COVID-19 in Adults 18 Years of Age and Older.
Official scientific title Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older. COVID-19
Brief summary describing the background and objectives of the trial An outbreak of severe respiratory illnesses in Wuhan City, Hubei Province, China in December 2019 heralded the appearance of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the human population. The rapid escalation of the outbreak led to a declaration by the World Health Organization on 20 January 2020 of a Public Health Emergency of International Concern, followed by the declaration on 11 March 2020 of a pandemic (1). As of 22 September 2020, the virus has been detected in 188 countries/regions and infected over 31.4 million individuals (2). To address the urgent medical need caused by this outbreak, Sanofi Pasteur is developing a candidate vaccine consisting of a stabilized prefusion trimer of the SARS-CoV-2 Spike (S) protein based on the work by Wrapp and colleagues (7). Sanofi Pasteur will apply the manufacturing technology that is used to produce recombinant influenza vaccine, which is commercialized in the United States (US), to rapidly develop a vaccine that can be supplied at a large multi-national scale. It is anticipated that the recombinant protein vaccine will require an adjuvant to optimize the immune response. AS03, an oil-in-water adjuvant supplied by GlaxoSmithKline, will be utilized for this vaccine development. References 1. World Health Organization. Virtual press conference on COVID-19 – 11 March 2020 [homepage on the Internet]. [cited 2020 Mar 28]. Available from: https://www.who.int/docs/default-source/coronaviruse/transcripts/who-audio-emergencies- coronavirus-press-conference-full-and-final-11mar2020.pdf?sfvrsn=cb432bb3_2. 2. Johns Hopkins School of Engineering. Coronavirus COVID-19 Global Cases by the Centers for Systems Science and Engineering (CSSE) at Johns Hopkins School of Engineering. [homepage on the Internet].[Last updated 2020 September 22. 9:23pm] [Cited 2020 September22]. Available from:http://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VAT00002
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Prevention
Anticipated trial start date 01/12/2020
Actual trial start date
Anticipated date of last follow up 30/04/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 34520
Actual target sample size (number of participants)
Recruitment status Withdrawn
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
Parallel: different groups receive different interventions at same time 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
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Placebo 0.5 mL per dose/2 injections 21 days apart Liquid, in a single-vial presentation 17260 Placebo
Experimental Group Vaccine 0.5 mL 2 injections / 21 days apart preS-delta TM monovalent: prefusion S delta TM COVID19 antigen, (placeholder: x-dose decided upon in VAT00001 [# µg]) AS03 adjuvant is composed of squalene (10.69 milligrams), DL-α- tocopherol (11.86 milligrams) and polysorbate 80 (4.86 milligrams). 17260
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants are eligible for the study only if all of the following criteria are met: I01: Aged 18 years or older on the day of inclusion I02: 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 vaccination until at least 12 weeks after the second vaccination. A subject of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 4 hours before any dose of study intervention. I03: Informed consent form has been signed and dated I04: Able to attend all scheduled visits and to comply with all trial procedures I05: Covered by health insurance, only if required by local, regional or national regulations I06: SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies I07: For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on ARVs with CD4 count > 200/mm3 Participants are not eligible for the trial if any of the following criteria are met: E01: Participation at the time of trial enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure E02: Receipt of any vaccine in the 30 days preceding or on the day of the first trial vaccination or planned receipt of any vaccine in the 30 days following the second trial vaccination except for influenza vaccination, which may be received at any time in relation to trial intervention a. E03: Prior administration of a coronavirus vaccine (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV]) E04: Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances b. E05: Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures based on Investigator or designee’s judgment E06: Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator or designee’s judgment E07: Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator or designee’s judgment E08: Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily E09: 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 trial procedures E10: Receipt of solid-organ or bone marrow transplants in the past 180 days E11: Receipt of anti-cancer chemotherapy in the last 90 days 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 99 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
No 06/11/2020 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Secondary Outcome 1.To assess, in adults who are SARS-CoV-2 naïve, the clinical efficacy of the investigational SARS-CoV-2 Recombinant Protein vaccine (with adjuvant) for: • Prevention of SARS-CoV-2 infection •Prevention of symptomatic COVID-19 with severity of severe COVID-19 or worse (composite endpoint of severe COVID-19 or critical COVID-19 or death due to COVID-19) 2.To assess the clinical efficacy of the investigational SARS-CoV-2 Recombinant Protein vaccine (with adjuvant) in SARS CoV-2 naïve adults for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the first injection. 3.To assess, in adults who are SARS-CoV-2 naïve, the clinical efficacy of investigational SARS-CoV-2 Recombinant Protein vaccine with adjuvant) for: • Prevention of asymptomatic SARS-CoV-2 infection • Reduction in duration of symptoms of symptomatic COVID-19 • Prevention of CDC-defined COVID-19 • Prevention of hospitalized symptomatic COVID-19 • Reduction in duration of hospitalization with symptomatic COVID-19 • Reduction in severity of symptomatic COVID-19 on the 7-point ordinal scale • Prevention of symptomatic COVID-19 with severity of moderate COVID-19 or worse (composite endpoint of moderate or severe COVIC-19 or critical COVID- 19 or death due to COVID-19) • Reduction in use of supplemental oxygen associated with symptomatic COVID- 19 • Prevention of symptomatic COVID-19 with severity of critical COVID-19 or death due to COVID-19 (composite endpoint of critical COVID-19 or death due to COVID-19) 14 days post dose 1 , 3,6,9 and 12 months.
Primary Outcome To assess the clinical efficacy of the investigational SARS-CoV-2 Recombinant Protein vaccine (with adjuvant) in SARS-CoV-2 naïve adults for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection. Occurrences of symptomatic COVID-19
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CRDC KEMRI CRDC Nairobi Kenya
KEMRI USAMRD Africa Kenya Kisumu Kisumu Kenya
Aga Khan University Hospital Nairobi Nairobi Kenya
KEMRI CGHR HIVR Division Kisumu Kisumu Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Sanofi Pasteur Sanofi Pasteur Inc. Discovery Drive, Swiftwater, PA 18370-0187, USA Philadelphia United States Minor Outlying Islands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor Sanofi Pasteur Sanofi Pasteur Inc. Discovery Drive, Swiftwater, PA 18370-0187, USA Swiftwater United States Minor Outlying Islands Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
GlaxoSmithKline UK UK United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Videlis Nduba vnduba@kemri.org +254724522474 KEMRI CRDC
City Postal code Country Position/Affiliation
Nairobi Kenya Principal Investigator KEMRI CRDC
Role Name Email Phone Street address
Scientific Enquiries Fabienne Roche Fabienne.Roche@sanofi.com +2710860160160 Sanofi House, 2 Bond Street, Grand Central Ext. 1, Midrand, 1685
City Postal code Country Position/Affiliation
Johannesburg South Africa Sponsor
Role Name Email Phone Street address
Public Enquiries Tirhani Maluleke Tirhani.Maluleke@sanofi.com +2710860160160 44 on Grand Central Office Park 2 Bond Street Grand Central Extension 1 Midrand 16
City Postal code Country Position/Affiliation
Johannesburg South Africa Sponsor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).A study protocol and a statistical analysis plan will also be shared. Timelines beginning 6-12 months and ending 5 years following article publication to anyone who wishes to access the data so as to make it known the aims of the approved proposal via a Sanofi Pasteur provided link. Study Protocol 12 Months Study end points
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 03/11/2020 Added COVID-19 tag as per WHOICTRP request Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older. Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older. COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 03/11/2020 correction to cover the full age range Adult: 19 Year-44 Year Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 03/11/2020 Additional Information A copy of the current study protocol has been attached with this submission. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).A study protocol and a statistical analysis plan will also be shared. Timelines beginning 6-12 months and ending 5 years following article publication to anyone who wishes to access the data so as to make it known the aims of the approved proposal via a Sanofi Pasteur provided link.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 08/04/2021 Phase 1/2 interim results showed an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years  Insufficient response in older adults demonstrates the need to refine the concentration of antigen in order to provide high-level immune response across all age groups  Companies plan a Phase 2b study with an improved antigen formulation  With support from BARDA as part of Operation Warp Speed, study to start in February 2021, including a proposed comparison with an authorized COVID-19 vaccine  Product availability now expected in Q4 2021 pending successful completion of the development plan Not yet recruiting Withdrawn