Study to Evaluate the Safety and the Immunogenicity of a Second Generation Structurally Designed mRNA Vaccine Candidate Against Pandemic Influenza H5 HA Strain in Healthy Adult Participants Aged 18 Years and Older

A Phase 1/2, Parallel-group, Randomized, Modified Double-blind, Placebo-controlled, Multi-center, Dose Ranging Study to Evaluate the Safety and Immunogenicity of a Second Generation Structurally Designed Pandemic Influenza H5 HA mRNA Vaccine in Healthy Adults Aged 18 Years and Older

The purpose of this phase 1/2 study is to investigate the safety and immunogenicity of different doses (high, medium and low) of a second generation structurally designed (SD2) H5 messenger ribonucleic acid (mRNA) vaccine against pandemic H5 influenza virus (pandemic flu H5 hemagglutinin (HA) mRNA SD2) in healthy younger and older adults.

The study will aim to identify the appropriate dose for further clinical development of a potential pandemic response vaccine.

The study also includes an extension phase for one of the 3 dose levels of the pandemic flu H5 HA mRNA SD2 vaccine to collect additional safety and the immunogenicity data for this specific dose of the vaccine. During this Extension Phase, an additional 480 participants will be randomized according to a 1:1 ratio and stratified by age (≥ 18 to < 65 years and ≥ 65 years) to receive either the low dose of the pandemic flu H5 HA mRNA DS2 vaccine (Group 1) or placebo (Group 4). This extension will enhance the safety database and improve precision of the immunogenicity results for the selected dose while preserving the original study design integrity.

The study duration per participant will be approximately 13 months. There will be two injections of placebo or pandemic flu H5 mRNA vaccine 21 days apart at high, medium and low doses.

Study visits/contact include: 7 study visits and 1 telephone call. Vaccination visits (including blood samples) will occur at Day 01 and Day 22. Short-term follow-up visits (including blood samples) will occur 8 and 21 days after each injection. Participants will be also followed up (including blood samples) at 3 and 6 months after 2nd injection, and at 12 months after 2nd injection for safety.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers; Pandemic Influenza Immunization
• Intervention / Treatment: Biological: Pandemic flu H5 HA mRNA SD2 vaccine; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 720
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research - San Diego- Site Number : 8400013
  • Florida
    • DeLand, Florida, United States, 32720
      • Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400002
    • Lakeland, Florida, United States, 33803
      • Accel Research Sites - Lakeland Clinical Research Unit- Site Number : 8400006
    • Largo, Florida, United States, 33777
      • Accel Research Sites - St. Petersburg - Largo- Site Number : 8400004
  • Georgia
    • Decatur, Georgia, United States, 30030-2627
      • Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400003
  • Michigan
    • Bingham Farms, Michigan, United States, 48334
      • QUEST Research Institute- Site Number : 8400014
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research - Norfolk- Site Number : 8400015
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research - Omaha- Site Number : 8400012
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Velocity Clinical Research - Springdale- Site Number : 8400010
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Coastal Carolina Research Center- Site Number : 8400001
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Olympus Clinical Research - Sugar Land- Site Number : 8400009
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research - Salt Lake City- Site Number : 8400011
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research- Site Number : 8400005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 must be postmenopausal 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 each study intervention administration until at least 12 weeks after the last study intervention administration

• A female 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 first dose of study intervention

Exclusion Criteria:

• 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)
• Known systemic hypersensitivity to any of the study intervention components (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of an mRNA vaccine
• Previous history of myocarditis, pericarditis, and/or myopericarditis
• Known history of previous episodes of Guillain-Barré Syndrome (GBS), neuritis (including Bell's palsy), convulsions , encephalitis, transverse myelitis, and vasculitis
• Participants with an electrocardiogram that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
• Self-reported thrombocytopenia, contraindicating IM injection based on investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM injection based on investigator's judgment
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
• Moderate or severe acute illness / infection (according to investigator's judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of study intervention. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
• Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
• Participant who had acute infectious symptoms or a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT PCR) or antigen test in the past 10 days prior to the first visit (V)01
• Receipt of any vaccine other than an mRNA vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine other than an mRNA vaccine in the 3 weeks following the second dose of the study intervention
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration or planned receipt of any mRNA vaccine in the 2 months after the second dose of the study intervention
• Participation at the time of study enrollment (or in the 4 weeks preceding study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Previous history of participation in an H5 influenza A vaccine study. This includes any influenza subtypes that contain H5 such as H5N1, H5N8, or H5N6

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2: Pandemic flu H5 HA mRNA SD2 vaccine (Medium dose); Participants will receive two injections of medium dose pandemic flu H5 HA mRNA SD2 vaccine	Biological: Pandemic flu H5 HA mRNA SD2 vaccine; Pharmaceutical Form: Suspension in a vial Route of Administration: Intramuscular injection
Experimental: Group 3: Pandemic flu H5 HA mRNA SD2 vaccine (High dose); Participants will receive two injections of high dose pandemic flu H5 HA mRNA SD2 vaccine	Biological: Pandemic flu H5 HA mRNA SD2 vaccine; Pharmaceutical Form: Suspension in a vial Route of Administration: Intramuscular injection
Experimental: Group 1: Pandemic flu H5 HA mRNA SD2 vaccine (Low dose); Participants will receive two injections of low dose pandemic flu H5 HA mRNA SD2 vaccine Extension Phase: Additional participants will receive two injections 21 days apart of pandemic flu H5 HA mRNA SD2 vaccine at low dose	Biological: Pandemic flu H5 HA mRNA SD2 vaccine; Pharmaceutical Form: Suspension in a vial Route of Administration: Intramuscular injection
Placebo Comparator: Group 4: Placebo; Participants will receive two injections of placebo Extension Phase: Additional participants will receive two injections 21 days apart of placebo	Other: Placebo; Pharmaceutical Form: Liquid solution in a vial Route of Administration: Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of immediate adverse events (AEs)	Number of participants with immediate AEs	Within 30 minutes after each/any injection
Presence of solicited injection site reactions	Number of participants with solicited injection site reactions	Through 7 days after each/any injection
Presence of solicited systemic reactions	Number of participants with solicited systemic reactions	Through 7 days after each/any injection
Presence of unsolicited AEs	Number of participants with unsolicited AEs	Through 21 days after the first injection through 28 days after the second injection
Presence of medically attended adverse events (MAAEs)	Number of participants with MAAEs	Through 180 days after the last injection
Presence of adverse events of special interest (AESIs)	Number of participants with AESIs	Throughout the study, approximately 13 months
Presence of serious adverse events (SAEs)	Number of participants with SAEs	Throughout the study, approximately 13 months
Presence of out-of-range biological test results (including shift from baseline values)	Number of participants with out-of-range biological test results	Through a maximum of 8 days after each injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers (GMTs) of antibodies (Abs) against investigational pandemic flu H5 HA mRNA SD2 vaccine	Ab titer measured by hemagglutination inhibition (HAI) assay	Day 01, Day 22, Day 43, Day 112 and Day 202
Individual HA titer ratio	Geometric mean ratio (GMR) HAI titers ratio	Day22/Day01, Day43/Day01, Day112/Day01, and Day202/Day01
Seroconversion HAI Titer	Percentage of participants with seroconversion Seroconversion is defined by: HAI titer < 10 [1/dilution (dil)] on Day 01 and post-injection titer ≥ 40 [1/dil] on Day 22 or Day 43; or defined as HAI titer ≥ 10 [1/dil] on D01 and a ≥ 4-fold increase in titer [1/dil]) on Day 22 or Day 43	Day 01, Day 22 and Day 43
HAI titer ≥ 40 (1/dil)	Percentage of participants with HAI titer ≥ 40 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202
Detectable HAI titer ≥ 10 (1/dil)	Percentage of participants with HAI titer ≥ 10 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202
GMTs of Abs against investigational pandemic flu H5 HA mRNA SD2 vaccine	Ab titer measured by seroneutralization (SN) test	Day 01, Day 22, Day 43, Day 112 and Day 202
Individual SN titer ratio	GMR SN titers ratio	Day 22/Day 02, Day 43/Day 01, Day 112/Day 01 and Day 202/Day 01
SN titer ≥ 20 (1/dil)	Percentage of participants with SN titer ≥ 20 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202
SN titer ≥ 40 (1/dil)	Percentage of participants with SN titer ≥ 40 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202
SN titer ≥ 80 (1/dil)	Percentage of participants with SN titer ≥ 80 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202
Detectable SN titer ≥ 10 (1/dil)	Percentage of participants with SN titer ≥ 10 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202
2-fold and 4-fold rise in SN titer	Percentage of participants with fold increase in SN Ab titer [post-vaccination / pre- vaccination] ≥ 2 and ≥ 4 on D22 and D43	Day 22 and Day 43

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• VBS00002 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pandemic Flu H5 Vaccination
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: VBS00002; U1111-1314-5493 (Other Identifier: WHO ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No