NCT04762680 - 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 | Crick | Crick

NCT04762680 - 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 | Crick | Crick

Interventions

SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage ABIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage BBIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 1BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 2BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 3BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 4BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03BIOLOGICAL

Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Immediate Unsolicited Adverse Events (AEs)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Immediate events were recorded to capture medically relevant unsolicited systemic AEs which occurred within the first 30 minutes after vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form (CRF) in terms of diagnosis and onset window post-vaccination.

Time frame: Up to 30 minutes after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)

Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Solicited Injection Site Reactions and Systemic Reactions

A solicited reaction was an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF, and were considered to be related to the study vaccine administered. An injection site reaction was an AR at and around the injection site of the study vaccine. Systemic AR were all ARs that were not injection site reactions.

Time frame: Up to 7 days after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)

Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Unsolicited Adverse Events

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.

Time frame: Up to 21 days after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)

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)

An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was 1 of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor could be appropriate. An MAAE was a new onset or a worsening of a condition that prompted the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.

Time frame: Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.

Phase 2: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) D614G Strain at Day 1

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Time frame: Pre-vaccination on Day 1

Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Day 36

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Time frame: Day 36

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

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers \>=2-fold and \>=4-fold increase from baseline (pre-vaccination) were analyzed.

Time frame: Day 1 (pre-vaccination) and Day 36

Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36

Responders were participants who had baseline values below lower limit of quantification (LLOQ) with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point.

Time frame: Day 36

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

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Time frame: Pre-vaccination on Day 1

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

Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Time frame: Cohorts 1 and 2: 14 days post-vaccination on Day 1, Day 15; Comparator: 14 days post-vaccination on Day 22, Day 36

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

Responders were participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Percentages are rounded off to the tenth decimal place.

Time frame: Day 36

Secondary Outcomes

Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.

Time frame: Post-vaccination on Days 22, 78, 134, 202, 292, and 387

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

Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers \>=2-fold and \>=4-fold increase from baseline (pre-vaccination) were analyzed.

Time frame: Pre-vaccination on Day 1 and Post-vaccination on Days 22, 78, 134, 202, 292, and 387

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

Responders were participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay).

Time frame: Post-vaccination on Days 22, 78, 134, 202, 292, and 387

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

Binding antibodies activity against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-enzyme-linked immunosorbent assay (ELISA) and the results were expressed as geometric mean titers.

Time frame: Pre-vaccination on Day 1 and post-vaccination on Days 22, 36, 78, 134, 202, 292, and 387

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