Clinical trial NCT04798027: Study of mRNA Vaccine Formulation Against COVID-19 in Healthy Adults 18 Years of Age and Older
Official title: Immunogenicity and Safety of the First-in-Human SARS-CoV-2 mRNA Vaccine Formulation in Healthy Adults 18 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 182
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 sequential group prevention study consisting of a sentinel cohort followed by the Full Enrollment Cohort. There were 3 dose levels (up to 25 participants 18-49 years of age for each dose level) in the Sentinel Cohort, which were done in an open-label fashion with stepwise safety evaluation for each dose level and each vaccination. All sentinel participants received 2 vaccinations, 21 days apart. For the Full Enrollment Cohort (FEC), which was done in a double-blind design participants were stratified into 2 groups based on age at enrollment: the younger adult age group (140 planned participants 18-49 years of age) and the older adult age group (168 planned participants greater than or equal to \[\>=\] 50 years of age). The FEC Cohort 1 (Groups 1 to 3) received a single injection of study intervention while participants in Cohort 2 (Groups 4 to 6) received 2 vaccinations (to be given 21 days apart).
Primary purpose: PREVENTION

Brief summary: The primary objectives of the study are:

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

The secondary objectives of the study are:

* To describe binding antibody profile from Day 1 to Day 387 of each study intervention group.
* To describe the neutralizing antibody profile from Day 91 to Day 387 of each study intervention group.
* To describe the occurrence of virologically-confirmed coronavirus disease-2019 (COVID-19)-like illness and serologically-confirmed SARS-CoV-2 infection.
* To evaluate the correlation/association between antibody responses to SARS-CoV-2 messenger RNA (mRNA) vaccine and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Detailed description: The duration of each participant's participation in the study was approximately 365 days post-last injection: approximately 386 days duration for participants receiving 2 injections and approximately 365 days duration total for participants receiving a single injection.

Eligibility criteria: Inclusion criteria:

* Aged \>= 18 years on the day of inclusion.
* A female participant was eligible to participate if she was not pregnant or breastfeeding and one of the following conditions applies:
* Was of non-childbearing potential. To be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, or surgically sterile.

OR

* Was of childbearing potential and agreed 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.

A participant of childbearing potential must had a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before the study intervention.

* Informed Consent Form had been signed and dated.
* Participant not eligible to receive, based on local guidance, or if eligible does not intend to receive an authorized/approved COVID-19 vaccine from first vaccination until completion of the key timepoint of Day 43 of follow-up of this study.

Exclusion criteria:

* History of COVID-19 disease or prior SARS-CoV-2 infection confirmed serologically.
* 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).
* Chronic illness or condition considered to potentially increase the risk for severe COVID illness or that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion.
* Known liver disease or fatty liver.
* Positive test for chronic active Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody from blood work collected at screening visit.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination based on Investigator's judgment.
* Receipt of immunoglobulins, blood or blood-derived products in the past 3 months.
* Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome coronavirus \[MERS-CoV\]).
* 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.
* Receipt of any therapy known to have in-vitro antiviral activity against SARS-CoV-2 within 72 hours prior to the first blood draw or planned use of such therapy 72 hours prior to study immunogenicity blood draws at Day 22 and Day 36.
* Residence in a nursing home or long-term care facility.
* Health care workers providing direct patient 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: Number of Participants Reporting 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 after 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 after any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Within 21 days after any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
measure: Number of Participants Reporting Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs)
timeFrame: From Day 1 until 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 groups and up to Day 387 for Cohort 2 groups)
measure: Number of Participants With Laboratory Test Results Based on US Food and Drug Administration (FDA) Toxicity Grading Guidance
timeFrame: From Day 1 up to up to 8 days post last vaccination (i.e., up to Day 9 for Cohort 1 groups; up to Day 30 for Cohort 2 groups)
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine at Day 1
timeFrame: Day 1 (pre-vaccination)
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine at Day 22
timeFrame: Day 22 (post-vaccination)
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine 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: Percentage 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: Percentage 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)
Secondary outcomes:
measure: Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 91, 112, 181, and 202
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2)
measure: Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 91, 112, 181, and 202
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2)
measure: Percentage of Participants With >=2- and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 91, 112, 181, and 202
timeFrame: Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2)
measure: Geometric Mean Titers of Neutralizing Antibody Titer Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 91, 112, 181, and 202
timeFrame: Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination)
measure: Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 91, 112, 181, and 202
timeFrame: Day 1 (pre-vaccination), Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination)
measure: Percentage of Participants With 2-Fold and 4-Fold Rise in Serum Neutralization Antibody Titer at Day 91, 112, 181, and 202
timeFrame: Day 1 (pre-vaccination), Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination)
measure: Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens
timeFrame: Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (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: Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination)
Other outcomes:
Locations:
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number :8400003
state: California
city: Hollywood
country: United States
facility: Investigational Site Number :8400002
state: Florida
city: Miami
country: United States
facility: Investigational Site Number :8400006
state: Florida
city: Iowa City
country: United States
facility: Investigational Site Number :8400017
state: Iowa
city: Kansas City
country: United States
facility: Investigational Site Number :8400007
state: Missouri
city: Omaha
country: United States
facility: Investigational Site Number :8400008
state: Nebraska
city: Rochester
country: United States
facility: Investigational Site Number :8400001
state: New York
city: Philadelphia
country: United States
facility: Investigational Site Number :8400010
state: Pennsylvania
city: North Charleston
country: United States
facility: Investigational Site Number :8400004
state: South Carolina
city: Knoxville
country: United States
facility: Investigational Site Number :8400015
state: Tennessee
city: Houston
country: United States
facility: Investigational Site Number :8400009
state: Texas
city: Salt Lake City
country: United States
facility: Investigational Site Number :8400005
state: Utah
city: Morayfield
country: Australia
facility: Investigational Site Number :0360003
state: Queensland
city: South Brisbane
country: Australia
facility: Investigational Site Number :0360005
state: Queensland
city: Melbourne
country: Australia
facility: Investigational Site Number :0360001
state: Victoria
city: Nedlands
country: Australia
facility: Investigational Site Number :0360002
state: Western Australia
city: Salvador
country: Brazil
facility: Investigational Site Number :0760001
state: Bahia
city: Campo Grande
country: Brazil
facility: Investigational Site Number :0760004
state: Mato Grosso Do Sul
city: Belo Horizonte
country: Brazil
facility: Investigational Site Number :0760003
state: Minas Gerais
city: Barrio Del Centro
country: Honduras
facility: Investigational Site Number :3400002
city: San Pedro Sula
country: Honduras
facility: Investigational Site Number :3400001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: