VAW00001: Study of mRNA Vaccine Formulation Against COVID-19 in Healthy Adults 18 Years of Age and Older

Sponsor

Sanofi Pasteur, a Sanofi Company (Industry)

Overall Status

Terminated

CT.gov ID

NCT04798027

Collaborator

(none)

182

Enrollment

Locations

Arms

15.5

Actual Duration (Months)

8.7

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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 90 to Day 387 of each study intervention group.
To describe the occurrence of virologically-confirmed COVID-19-like illness and serologically-confirmed SARS-CoV-2 infection.
To evaluate the correlation/association between antibody responses to SARS-CoV-2 mRNA vaccine and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed SARS-CoV-2 infection.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: SARS-CoV-2 mRNA vaccine formulation 1 Biological: SARS-CoV-2 mRNA vaccine formulation 2 Biological: SARS-CoV-2 mRNA vaccine formulation 3 Biological: Placebo (0.9% normal saline)	Phase 1/Phase 2

Detailed Description

The duration of each participant's participation in the study will be 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

182 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a sequential group prevention study consisting of a sentinel cohort followed by the Full Enrollment Cohort. There will be 3 dose levels (up to 25 participants 18-49 years of age for each dose level) in the Sentinel Cohort, which will be done in an open-label fashion with stepwise safety evaluation for each dose level and each vaccination. All sentinel participants will receive 2 vaccinations, 21 days apart. For the Full Enrollment Cohort, participants will be stratified into 2 age groups based on age at enrollment: the younger adult age group (140 participants 18-49 years of age) and the older adult age group (168 participants ≥ 50 years of age). The Full Enrollment Cohort 1 (Groups 1 to 4) will receive a single injection of study intervention while participants in Cohort 2 (Groups 5 to 8) will receive 2 vaccinations (to be given 21 days apart).This is a sequential group prevention study consisting of a sentinel cohort followed by the Full Enrollment Cohort. There will be 3 dose levels (up to 25 participants 18-49 years of age for each dose level) in the Sentinel Cohort, which will be done in an open-label fashion with stepwise safety evaluation for each dose level and each vaccination. All sentinel participants will receive 2 vaccinations, 21 days apart. For the Full Enrollment Cohort, participants will be stratified into 2 age groups based on age at enrollment: the younger adult age group (140 participants 18-49 years of age) and the older adult age group (168 participants ≥ 50 years of age). The Full Enrollment Cohort 1 (Groups 1 to 4) will receive a single injection of study intervention while participants in Cohort 2 (Groups 5 to 8) will receive 2 vaccinations (to be given 21 days apart).

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

In the Full Enrollment Cohort: blinding for vaccine group assignment (formulation) of participants, outcome assessors, Investigators, laboratory personnel, and Sponsor study staff. Only study site staff who prepare and administer the vaccine and are not involved with the safety evaluations will be unblinded to vaccine group assignment. There will be no blinding for injection schedule. The Sentinel Cohort is open-label (no blinding).

Primary Purpose:

Prevention

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

Actual Study Start Date :

Mar 12, 2021

Actual Primary Completion Date :

Jun 27, 2022

Actual Study Completion Date :

Jun 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 1 injection of SARS-CoV-2 mRNA vaccine formulation 1 at Day 1	Biological: SARS-CoV-2 mRNA vaccine formulation 1 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Experimental: Group 2 1 injection of SARS-CoV-2 mRNA vaccine formulation 2 at Day 1	Biological: SARS-CoV-2 mRNA vaccine formulation 2 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Experimental: Group 3 1 injection of SARS-CoV-2 mRNA vaccine formulation 3 at Day 1	Biological: SARS-CoV-2 mRNA vaccine formulation 3 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Placebo Comparator: Group 4 1 injection of placebo at Day 1	Biological: Placebo (0.9% normal saline) Pharmaceutical form: Liquid Route of administration: Intramuscular injection
Experimental: Group 5 2 injections of SARS-CoV-2 mRNA vaccine formulation 1 at Day 1 and Day 22	Biological: SARS-CoV-2 mRNA vaccine formulation 1 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Experimental: Group 6 2 injections of SARS-CoV-2 mRNA vaccine formulation 2 at Day 1 and Day 22	Biological: SARS-CoV-2 mRNA vaccine formulation 2 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Experimental: Group 7 2 injections of SARS-CoV-2 mRNA vaccine formulation 3 at Day 1 and Day 22	Biological: SARS-CoV-2 mRNA vaccine formulation 3 Pharmaceutical form: Sterile suspension Route of administration: Intramuscular injection
Placebo Comparator: Group 8 2 injections of placebo at Day 1 and Day 22	Biological: Placebo (0.9% normal saline) Pharmaceutical form: Liquid Route of administration: Intramuscular injection

Outcome Measures

Primary Outcome Measures

Presence of immediate adverse events [Within 30 minutes after vaccination]
Immediate adverse events include unsolicited systemic adverse events occurring within 30 minutes after vaccination
Presence of solicited injection site reactions and systemic reactions [Within 7 days after vaccination]
Injection site reactions: injection site pain, erythema and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills.
Presence of unsolicited adverse events [Within 21 days after vaccination]
Adverse events other than solicited reactions.
Presence of medically attended adverse events [From Day 1 to Day 387]
A medically attended adverse event is a new-onset or a worsening of a condition that prompts the participant to seek unplanned medical advice at a physician's office or Emergency Department
Presence of serious adverse events (SAE) and adverse events of special interest (AESI) [From Day 1 to Day 387]
SAEs are collected throughout the study.
Presence of out-of-range biological test results [From Day 1 up to 8 days post-last injection]
Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test) are considered. The assessment include white blood cell count, hemoglobin, platelet count, clinical chemistry parameters, and coagulation parameters.
Neutralizing antibody titer [From Day 1 to Day 36]
Neutralizing antibody titers expressed as geometric mean titers.
Fold-rise in neutralizing antibody titer [From Day 1 to Day 36]
Fold-rise in serum neutralization titer post-vaccination relative to Day 1
2-fold and 4-fold rise in neutralizing antibody titer [From Day 1 to Day 36]
Fold-rise relative to Day 1.
Occurrence of neutralizing antibody seroconversion [From Day 1 to Day 36]
Seroconversion is defined as baseline values below lower limit of quantification (LLOQ) with detectable neutralization titer above assay LLOQ post-vaccination

Secondary Outcome Measures

Binding antibody concentration [From Day 1 to Day 387]
Binding antibody concentration ratio [From Day 1 to Day 387]
Fold-rise in binding antibody concentration postvaccination relative to Day 1
Fold-rise in binding antibody concentration (post/pre) ≥ 2 and ≥ 4 [From Day 1 to Day 387]
Neutralizing antibody titers at Day 91 to Day 387 [From Day 91 to Day 387]
Fold-rise in neutralizing antibody titer at Day 91 to Day 387 [From Day 91 to Day 387]
Fold-rise in serum neutralization titer post-vaccination relative to Day 1
2-fold and 4-fold rise in neutralizing antibody titer at Day 91 to Day 387 [From Day 91 to Day 387]
Occurrence of neutralizing antibody seroconversion at Day 91 to Day 387 [From Day 91 to Day 387]
Seroconversion is defined as baseline values below LLOQ with detectable neutralization titer above assay LLOQ post-vaccination
Occurrences of virologically-confirmed COVID-19-like illness [From Day 1 to Day 387]
Virologically-confirmed COVID-19-like illness is defined as a positive result for SARS CoV-2 by Nucleic Acid Amplification Test (NAAT) on a respiratory sample in association with a COVID-19-like illness
Occurrences of serologically-confirmed SARS-CoV-2 infection [From Day 1 to Day 387]
Serologically-confirmed COVID-19-like illness is defined as a positive result in serum for the presence of antibodies specific to SARS-CoV-2 detected by immunoassay
Correlates of risk/protection based on antibody responses to SARS-CoV-2 [From Day 1 to Day 387]
Correlate analysis considering virologically-confirmed COVID-19-like illness and/or serologically confirmed SARS CoV 2 infection

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria :

Aged ≥ 18 years 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 must be pre-menarche or post-menopausal for at least 1 year, or surgically sterile.

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.

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

Informed Consent Form has 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 severe acute respiratory syndrome coronavirus 2 (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 immuneglobulins, 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 may 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 patients.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :8400003	Rolling Hills Estates	California	United States	90274
2	Investigational Site Number :8400002	Hollywood	Florida	United States	33024
3	Investigational Site Number :8400006	Miami	Florida	United States	33135
4	Investigational Site Number :8400017	Iowa City	Iowa	United States	52242
5	Investigational Site Number :8400007	Kansas City	Missouri	United States	64114
6	Investigational Site Number :8400008	Omaha	Nebraska	United States	68134
7	Investigational Site Number :8400001	Rochester	New York	United States	14609
8	Investigational Site Number :8400010	Philadelphia	Pennsylvania	United States	19104
9	Investigational Site Number :8400004	North Charleston	South Carolina	United States	29405
10	Investigational Site Number :8400015	Knoxville	Tennessee	United States	37920
11	Investigational Site Number :8400009	Houston	Texas	United States	77081
12	Investigational Site Number :8400005	Salt Lake City	Utah	United States	84107
13	Investigational Site Number :0360003	Morayfield	Queensland	Australia	4506
14	Investigational Site Number :0360005	South Brisbane	Queensland	Australia	4101
15	Investigational Site Number :0360001	Melbourne	Victoria	Australia	3010
16	Investigational Site Number :0360002	Nedlands	Western Australia	Australia	6009
17	Investigational Site Number :0760001	Salvador	Bahia	Brazil	40415-006
18	Investigational Site Number :0760004	Campo Grande	Mato Grosso Do Sul	Brazil	79070-900
19	Investigational Site Number :0760003	Belo Horizonte	Minas Gerais	Brazil	30110-063
20	Investigational Site Number :3400002	Municipio Del Distrito Central		Honduras	11101
21	Investigational Site Number :3400001	San Pedro Sula		Honduras	21104

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi Pasteur, a Sanofi Company

ClinicalTrials.gov Identifier:

NCT04798027

Other Study ID Numbers:

VAW00001
U1111-1251-5486

First Posted:

Mar 15, 2021

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

COVID-19

Vaccines

Study Results

No Results Posted as of Aug 25, 2022