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

NCT06907511 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: VBS00002U1111-1314-5493
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Pandemic Influenza Immunization; Healthy Volunteers

Keywords

Pandemic Flu H5 Vaccination

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (12)

• Geometric mean titers (GMTs) of antibodies (Abs) against investigational pandemic flu H5 HA mRNA SD2 vaccine

  Day 01, Day 22, Day 43, Day 112 and Day 202

• Individual HA titer ratio

  Day22/Day01, Day43/Day01, Day112/Day01, and Day202/Day01

• Seroconversion HAI Titer

  Day 01, Day 22 and Day 43

• HAI titer ≥ 40 (1/dil)

  Day 01, Day 22, Day 43, Day 112, and Day 202

• Detectable HAI titer ≥ 10 (1/dil)

  Day 01, Day 22, Day 43, Day 112, and Day 202

Study Arms (4)

Group 1: Pandemic flu H5 HA mRNA SD2 vaccine (Low dose)

EXPERIMENTAL

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

Group 2: Pandemic flu H5 HA mRNA SD2 vaccine (Medium dose)

EXPERIMENTAL

Participants will receive two injections of medium dose pandemic flu H5 HA mRNA SD2 vaccine

Biological: Pandemic flu H5 HA mRNA SD2 vaccine

Group 3: Pandemic flu H5 HA mRNA SD2 vaccine (High dose)

EXPERIMENTAL

Participants will receive two injections of high dose pandemic flu H5 HA mRNA SD2 vaccine

Biological: Pandemic flu H5 HA mRNA SD2 vaccine

Group 4: Placebo

PLACEBO COMPARATOR

Participants will receive two injections of placebo Extension Phase: Additional participants will receive two injections 21 days apart of placebo

Other: Placebo

Interventions

Placebo OTHER

Pharmaceutical Form: Liquid solution in a vial Route of Administration: Intramuscular injection

Group 4: Placebo

Pandemic flu H5 HA mRNA SD2 vaccine BIOLOGICAL

Pharmaceutical Form: Suspension in a vial Route of Administration: Intramuscular injection

Group 1: Pandemic flu H5 HA mRNA SD2 vaccine (Low dose); Group 2: Pandemic flu H5 HA mRNA SD2 vaccine (Medium dose); Group 3: Pandemic flu H5 HA mRNA SD2 vaccine (High dose)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Velocity Clinical Research - San Diego- Site Number : 8400013

La Mesa, California, 91942, United States

Location

Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400002

DeLand, Florida, 32720, United States

Location

Accel Research Sites - Lakeland Clinical Research Unit- Site Number : 8400006

Lakeland, Florida, 33803, United States

Location

Accel Research Sites - St. Petersburg - Largo- Site Number : 8400004

Largo, Florida, 33777, United States

Location

Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400003

Decatur, Georgia, 30030-2627, United States

Location

QUEST Research Institute- Site Number : 8400014

Bingham Farms, Michigan, 48334, United States

Location

Velocity Clinical Research - Norfolk- Site Number : 8400015

Norfolk, Nebraska, 68701, United States

Location

Velocity Clinical Research - Omaha- Site Number : 8400012

Omaha, Nebraska, 68134, United States

Location

Velocity Clinical Research - Springdale- Site Number : 8400010

Cincinnati, Ohio, 45246, United States

Location

Coastal Carolina Research Center- Site Number : 8400001

North Charleston, South Carolina, 29406, United States

Location

Olympus Clinical Research - Sugar Land- Site Number : 8400009

Sugar Land, Texas, 77479, United States

Location

Velocity Clinical Research - Salt Lake City- Site Number : 8400011

West Jordan, Utah, 84088, United States

Location

Charlottesville Medical Research- Site Number : 8400005

Charlottesville, Virginia, 22911, United States

Location

Related Links

• VBS00002 Plain Language Results Summary

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double-blind (participants; sites, except for those preparing/administering study intervention; and Sponsor will be blinded).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 2, 2025
• Study Start: April 17, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (13)