Study of Recombinant Protein Vaccines With Adjuvant as a Primary Series and as a Booster Dose Against COVID-19 in Adults 18 Years of Age and Older
Purpose
The primary objectives of the study are: To assess the safety profile of the study vaccines in each study intervention group. To assess the neutralizing antibody profile after primary series vaccination in SARS-CoV-2-naïve adults. To demonstrate that a booster dose of monovalent or bivalent SARS-CoV-2 vaccine given to adults previously vaccinated with an authorized/approved COVID-19 vaccine induces an immune response that is non-inferior to the response induced by a twodose priming series with the monovalent vaccine, and superior to that observed immediately before booster. The secondary objectives of the study are: To assess the neutralizing and binding antibody profiles after primary series vaccination at pre-defined time points during the study. To assess the neutralizing and binding antibody responses of booster vaccination. To describe the occurrences of laboratory-confirmed symptomatic COVID19 after primary series and booster vaccination. To describe the occurrences of serologically-confirmed SARS-CoV-2 infection after primary series vaccination.
Condition
- COVID-19
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Aged 18 years or older on the day of inclusion. - -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 mut 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 last vaccination (ie, second dose of primary series or booster injection). A participant 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. - -Informed consent form has been signed and dated. Able to attend all scheduled visits and to comply with all study procedures. SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies (Original Phase 2 Cohort). For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3. Does not intend to receive an authorized/approved COVID-19 vaccine from first vaccination to 3 weeks after the second vaccination despite encouragement by the investigator to receive the authorized vaccine available to them at the time of enrollment. Supplemental cohorts: for participants originally enrolled in the Phase II cohort of the study, informed consent has to be signed and dated for transitioning to Supplemental Cohort 2. Supplemental cohorts, Booster arms: received a complete primary vaccination series with an authorized/conditionally approved mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer/BioNTech]) or adenovirus-vectored COVID-19 vaccine (ChAdOx1 nCoV-19 [Oxford University/AstraZeneca] or Ad26.CoV2.S [J&J/Janssen]), with the last dose administered a minimum of 4 months prior to inclusion but not longer than 10 months prior to inclusion.
Exclusion Criteria
- 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. Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures based on Investigator or designee's judgment. Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator's judgment. Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator's judgment. 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. Receipt of solid-organ or bone marrow transplants in the past 180 days. Receipt of anti-cancer chemotherapy in the last 90 days. Receipt of immunoglobulins, blood, or blood-derived products in the past 3 months. 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 trial until the condition has resolved or the febrile event has subsided. 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. Applicable to Original Phase II Cohort, Supplemental Cohort 1 and Cohort 2 Comparator Group: Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV]). Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study trial period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Exclusion criterion for the Supplemental Cohort 1 and Cohort 2 comparator group: positive rapid diagnostic test for SARS-CoV-2 antibodies at time of enrollment. Exclusion criterion for participants in Supplemental Cohort 2 who were primed as participant in the Original Phase II Cohort of the present study: Receipt of authorized/conditionally approved COVID-19 vaccine after enrollment in Original Phase 2 Cohort. Exclusion criterion for all Booster groups: Documented virologically-confirmed SARS-CoV-2 infection (by NAAT) after first dose of primary immunization.
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- To address the emergence of variant strains, Sanofi Pasteur is developing monovalent and bivalent vaccines for use as universal late booster vaccines which will be studied in additional Phase 3 study cohorts that are added to the initial Phase 2 protocol cohorts. Supplemental Cohorts 1 and 2 will evaluate booster vaccine candidates.
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- In the original Phase 2 part, participants, outcome assessors, Investigators, laboratory personnel, and sponsor study staff are blinded to intervention group; and those preparing the study interventions are unblinded to vaccine assignment group. The supplemental Cohort 1 intervention group and Supplemental Cohorts Comparator Group will be open-label. Supplemental Cohort 2 will involve sequential randomization to main arms then exploratory arms, and the intervention will be modified double-blind (observer-blinded, as described).
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 2 Cohort -SARS-CoV-2 vaccine Formulation 1 |
2 injections of SARS-CoV-2 vaccine Formulation 1 at Day 1 and Day 22 |
|
|
Experimental Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 2 |
2 injections of SARS-CoV-2 vaccine Formulation 2 at Day 1 and Day 22 |
|
|
Experimental Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 3 |
2 injections of SARS-CoV-2 vaccine Formulation 3 Day 1 and Day 22 |
|
|
Experimental Supplemental Cohort 1 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine |
Participants who were previously vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine will receive 1 booster injection of monovalent (D614)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Supplemental Cohort 2 - Booster Monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine or SARS-Cov-2 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Supplemental Cohort 2 - Booster Bivalent (D614 + B.1.351)-AS03 SARS-CoV-2 vaccine |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine will receive 1 booster injection of bivalent (D614+B.1.351)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Supplemental Cohort 2 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine |
Participants who were vaccinated 4 to < 10 months prior with SARS-Cov-2 vaccine will receive 1 booster injection of monovalent (D614)-AS03 SARS-CoV-2 vaccine |
|
|
Active Comparator Supplemental Comparator for Cohort 1 and 2 Boosters - Monovalent (D614)-AS03 SARS-CoV-2 vaccine |
2 injections of monovalent (D614)-AS03 SARS-CoV-2 vaccine at Day 1 and Day 22 in previously unvaccinated, naïve participants |
|
|
Experimental Cohort 2 - Booster Exploratory 1 |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Cohort 2 - Booster Exploratory 2 |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Cohort 2 - Booster Exploratory 3 |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
|
|
Experimental Cohort 2 - Booster Exploratory 4 |
Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine |
|
Recruiting Locations
More Details
- NCT ID
- NCT04762680
- Status
- Active, not recruiting
- Sponsor
- Sanofi Pasteur, a Sanofi Company
Detailed Description
The duration of each participant's participation in the study will be approximately: Original Phase 2 part: 365 days postinjection 2 (ie, 386 days total). Supplemental Cohorts 1 and 2: 365 days post-booster injection (ie, 366 days total).