Clinical trial NCT04537208: Study of Recombinant Protein Vaccine Formulations Against COVID-19 in Healthy Adults 18 Years of Age and Older
Official title: Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine Formulations (With or Without Adjuvant) in Healthy Adults 18 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19 (Healthy Volunteers)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2020-09-03
Enrollment: 441
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a parallel group prevention study. Participants from 2 age groups (adults 18 through 49 years of age and adults 50 years of age and older) received either 1 injection (Cohort 1) or 2 injections (Cohort 2) of study vaccine or placebo control.

As a precautionary step, a sentinel safety cohort of 6 participants (younger adults only) within each dosing group from Cohort 1 was enrolled. An early safety data review was performed, including evaluation of safety data and laboratory measures to Day 9. Upon acceptable safety demonstrated from unblinded data review by limited members of the Sponsor Study Team, the remaining participants were enrolled simultaneously.
Primary purpose: PREVENTION

Brief summary: The primary objectives of the study were:

* To describe the neutralizing antibody profile at Day 1, Day 22, and Day 36 of each study intervention group.
* To describe the safety profile of all participants in each age group and each study intervention group up to 12 months post-last injection.

The secondary objectives of the study are:

* To describe binding antibody profile at Day 1, Day 22, Day 36, Day 181 (Cohort 1) or Day 202 (Cohort 2), and Day 366 (Cohort 1) or Day 387 (Cohort 2) of each study intervention group.
* To describe the neutralizing antibody profile at Day 181 (Cohort 1) or Day 202 (Cohort 2) and at Day 366 (Cohort 1) and Day 387 (Cohort 2) of each study intervention group.
* To describe the occurrence of virologically-confirmed coronavirus disease (COVID-19)-like illness and serologically-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
* To evaluate the correlation / association between antibody responses to SARS-CoV-2 Recombinant Protein and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed SARS-CoV-2 infection.

Detailed description: The duration of each participant's participation in the study was approximately 365 days (Cohort 1) and 386 days (Cohort 2) post last injection.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years of age or older on the day of inclusion.
* Informed consent form had been signed and dated.
* Able to attend all scheduled visits and complied with all study procedures.

Exclusion Criteria:

* Participant was pregnant, or lactating, or of childbearing potential and not used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination. To be considered of non-childbearing potential, a female was post-menopausal for at least 1 year or surgically sterile.
* Receipt of any vaccine in the 30 days preceding the first study vaccination or planned receipt of any vaccine in the 30 days following the last study vaccination except for influenza vaccination, which might be received at least 2 weeks before and a minimum of 2 weeks after study vaccines.
* Prior administration of a coronavirus vaccine SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
* History of SARS-CoV-2 infection, confirmed either clinically, serologically, or microbiologically
* Chronic illness or condition considered to potentially increase the risk for severe COVID illness or that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
* Receipt of any therapy known to had in-vitro antiviral activity against SARS-CoV-2 within 72 hours prior to the first blood drew.
* Health care workers provided direct participant care for COVID-19 participants.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 1
timeFrame: Day 1 (pre-vaccination)
measure: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 22
timeFrame: Day 22 (post-vaccination)
measure: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 36
timeFrame: Day 36 (post-vaccination)
measure: Geometric Mean Fold-rise (GMFR) of Serum Neutralization Antibody Titers at Day 22
timeFrame: Day 1 (pre-vaccination) and Day 22 (post-vaccination)
measure: Geometric Mean Fold-rise of Serum Neutralization Antibody Titers at Day 36
timeFrame: Day 1 (pre-vaccination) and Day 36 (post-vaccination)
measure: Number of Participants With >=2-fold and >=4-fold Rise in Serum Neutralization Antibody Titers at Day 22
timeFrame: Day 1 (pre-vaccination) and Day 22 (post-vaccination)
measure: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titer at Day 36
timeFrame: Day 1 (pre-vaccination) and Day 36 (post-vaccination)
measure: Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 22
timeFrame: Day 22 (post-vaccination)
measure: Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 36
timeFrame: Day 36 (post-vaccination)
measure: Number of Participants With Immediate Unsolicited Adverse Events (AEs)
timeFrame: Within 30 minutes post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Within 7 days post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
measure: Number of Participants With Solicited Systemic Reactions
timeFrame: Within 7 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Within 21 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])
measure: Number of Participants With Medically Attended Adverse Events (MAAE)
timeFrame: From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
measure: Number of Participants With Serious Adverse Events (SAE)
timeFrame: From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
measure: Number of Participants With Laboratory Test Results Based on US FDA Toxicity Grading Guidance
timeFrame: From Day 1 up to 8 days post last dose (i.e., up to Day 9 for Cohort 1 and up to Day 30 for Cohort 2)
Secondary outcomes:
measure: Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 181, 202, 366 and 387
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
measure: Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
measure: Number of Participants With >=2-Fold and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
measure: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 181, 202, 366 and 387
timeFrame: Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
measure: Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
timeFrame: Day 1 (pre-vaccination), Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
measure: Number of Participants With 2-Fold and 4-Fold Rise in Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
timeFrame: Day 1 (pre-vaccination), Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
measure: Percentage of Participants Achieving Seroconversion Against SARS-CoV2 Virus Antigens at Day 181, 202, 366 and 387
timeFrame: Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
measure: Number of Participants With Virologically-confirmed Coronavirus Disease (COVID-19)-Like Illness
timeFrame: Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination)
measure: Number of Participants With Serologically-confirmed SARS-CoV-2 Infection
timeFrame: Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination)
measure: Correlates of Risk / Protection Based on Antibody Responses to SARS-CoV-2
timeFrame: From Day 1 up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8400004
state: Alabama
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 8400012
state: California
city: Hollywood
country: United States
facility: Investigational Site Number 8400011
state: Florida
city: Melbourne
country: United States
facility: Investigational Site Number 8400019
state: Florida
city: Boston
country: United States
facility: Investigational Site Number 8400016
state: Massachusetts
city: Omaha
country: United States
facility: Investigational Site Number 8400002
state: Nebraska
city: Rochester
country: United States
facility: Investigational Site Number 8400001
state: New York
city: Rochester
country: United States
facility: Investigational Site Number 8400007
state: New York
city: Cleveland
country: United States
facility: Investigational Site Number 8400008
state: Ohio
city: Philadelphia
country: United States
facility: Investigational Site Number 8400003
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Investigational Site Number 8400014
state: South Carolina
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: De Rosa SC, Cohen KW, Bonaparte M, Fu B, Garg S, Gerard C, Goepfert PA, Huang Y, Larocque D, McElrath MJ, Morris D, Van der Most R, de Bruyn G, Pagnon A. Whole-blood cytokine secretion assay as a high-throughput alternative for assessing the cell-mediated immunity profile after two doses of an adjuvanted SARS-CoV-2 recombinant protein vaccine candidate. Clin Transl Immunology. 2022 Jan 11;11(1):e1360. doi: 10.1002/cti2.1360. eCollection 2022.
citation: Goepfert PA, Fu B, Chabanon AL, Bonaparte MI, Davis MG, Essink BJ, Frank I, Haney O, Janosczyk H, Keefer MC, Koutsoukos M, Kimmel MA, Masotti R, Savarino SJ, Schuerman L, Schwartz H, Sher LD, Smith J, Tavares-Da-Silva F, Gurunathan S, DiazGranados CA, de Bruyn G. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. Lancet Infect Dis. 2021 Sep;21(9):1257-1270. doi: 10.1016/S1473-3099(21)00147-X. Epub 2021 Apr 19.