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
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT04762680 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1 (Biological); SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2 (Biological); SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage B (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 1 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 2 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 3 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 4 (Biological); SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03 (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sanofi Pasteur, a Sanofi Company
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Immediate Unsolicited Adverse Events (AEs) |
2; 1; 1; 0; 0; 0 | — |
| PRIMARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Solicited Injection Site Reactions and Systemic Reactions |
201; 196; 200; 262; 300; 303 | — |
| PRIMARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Unsolicited Adverse Events |
88; 81; 91; 76; 106; 96 | — |
| PRIMARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs) |
2; 6; 4; 8; 9; 11 | — |
| PRIMARY Phase 2: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) D614G Strain at Day 1 |
20.0; 20.0; 20.0 | — |
| PRIMARY Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Day 36 |
2132; 2376; 2903 | — |
| PRIMARY Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36 |
155; 156; 158; 154; 154; 157 | — |
| PRIMARY Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36 |
155; 156; 158 | — |
| PRIMARY Phase 3: Cohorts 1 and 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Day 1 |
320; 678; 579; 668; 1107; 1347 | — |
| PRIMARY Phase 3: Cohorts 1, 2 and Comparator: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at 14 Days Post-Vaccination |
6964; 9995; 8430; 6347; 14240; 12522 | — |
| PRIMARY Phase 3: Comparator: Percentage of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Day 36 |
99.3; 91.0 | — |
| SECONDARY Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387 |
36.0; 39.6; 47.3; 467; 558; 569 | — |
| SECONDARY Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387 |
35; 44; 53; 28; 36; 44 | — |
| SECONDARY Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387 |
35; 44; 53; 108; 116; 113 | — |
| SECONDARY Phase 2: Geometric Mean Concentration (GMC) of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 22, 36, 78, 134, 202, 292, and 387 |
10.3; 9.99; 10.2; 103; 149; 228 | — |
| SECONDARY Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 78, 134, 202, 292, and 387 |
141; 155; 161; 117; 136; 156 | — |
| SECONDARY Phase 2: Number of Responders as Determined by Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 78, 134, 202, 292, and 387 |
139; 154; 161; 159; 160; 165 | — |
| SECONDARY Phase 3: Cohort 1: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 29, 91, 181, and 366 |
5795; 5743; 4869; 4400; 2078; 1726 | — |
| SECONDARY Phase 3: Cohort 1: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 15, 29, 91, 181, and 366 |
263; 86; 95; 70; 252; 70 | — |
| SECONDARY Phase 3: Cohorts 1, 2 and Comparator: Percentage of Participants With Seroresponse Against SARS-CoV-2 D614G Strain and B.1.351 Variant at 14 Days Post-Vaccination |
90.6; 73.7; 75.6; 71.4; 72.8; 63.7 | — |
| SECONDARY Phase 3: Cohorts 1 and 2: Geometric Mean Concentration of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 15, 29, 91, 181, and 366 |
1888; 3032; 2580; 3236; 3285; 3505 | — |
| SECONDARY Phase 3: Cohorts 1 and 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 15, 29, 91, 181, and 366 |
287; 276; 292; 94; 84; 87 | — |
| SECONDARY Phase 3: Cohort 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 1, 15, 29, and 91 |
678; 579; 1107; 1347; 137; 134 | — |
| SECONDARY Phase 3: Cohort 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 15, 29, and 91 |
267; 269; 79; 77; 85; 84 | — |
| SECONDARY Phase 3: Comparator: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 1, 22, 36, 134, 202, 292, and 387 |
20.3; 53.3; 3658; 1050; 1685; 1943 | — |
| SECONDARY Phase 3: Comparator: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 22, 36, 134, 202, 292, and 387 |
99; 88; 299; 298; 134; 131 | — |
| SECONDARY Phase 3: Comparator: Geometric Mean Concentration of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 22, 36, 134, 202, 292, and 387 |
10.7; 212; 24278; 6593; 6667; 6868 | — |
| SECONDARY Phase 3: Comparator: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 134, 202, 292, and 387 |
312; 290; 302; 302; 149; 148 | — |
| SECONDARY Phase 3: Comparator: Percentage of Responders as Determined by Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 134, 202, 292, and 387 |
94.3; 99.7; 98.7; 99.3; 99.3; 99.2 | — |
| SECONDARY Phase 2: Percentage of Participants With Serologically-Confirmed SARS-CoV-2 Infection |
12.1; 10.8; 14.1 | — |
| SECONDARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Laboratory-Confirmed Symptomatic COVID-19 |
3.3; 1.7; 5.4; 14.0; 20.9; 23.5 | — |
| SECONDARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Symptomatic COVID-19 Episodes Associated With Hospitalization |
0; 0; 0; 0; 0; 0.3 | — |
| SECONDARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Severe Symptomatic COVID-19 |
0; 0; 0; 0; 0; 0.3 | — |
| SECONDARY Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Death Associated With Symptomatic COVID-19 |
0; 0; 0; 0; 0; 0 | — |
Summary
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04762680). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.