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

Phase 1

Active, not recruiting

• Conditions: Pandemic Influenza Immunization; Healthy Volunteers
• Interventions: Biological: Pandemic flu H5 HA mRNA SD2 vaccine; Other: Placebo

• Registration Number: NCT06907511
• Lead Sponsor: Sanofi

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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-26
• Study First Submitted QC: 2025-03-26
• Study First Posted: 2025-04-02
• Study Start: 2025-04-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2026-05-28
• Study Completion: 2026-05-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 240

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Pandemic flu H5 HA mRNA SD2 vaccine (Low dose)	Pandemic flu H5 HA mRNA SD2 vaccine	Participants will receive two injections of low dose pandemic flu H5 HA mRNA SD2 vaccine
Group 2: Pandemic flu H5 HA mRNA SD2 vaccine (Medium dose)	Pandemic flu H5 HA mRNA SD2 vaccine	Participants will receive two injections of medium dose pandemic flu H5 HA mRNA SD2 vaccine
Group 3: Pandemic flu H5 HA mRNA SD2 vaccine (High dose)	Pandemic flu H5 HA mRNA SD2 vaccine	Participants will receive two injections of high dose pandemic flu H5 HA mRNA SD2 vaccine
Placebo	Placebo	Participants will receive two injections of placebo

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Ab titer measured by hemagglutination inhibition (HAI) assay
Individual HA titer ratio	Day22/Day01, Day43/Day01, Day112/Day01, and Day202/Day01	Geometric mean ratio (GMR) HAI titers ratio
Seroconversion HAI Titer	Day 01, Day 22 and Day 43	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
HAI titer ≥ 40 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202	Percentage of participants with HAI titer ≥ 40 (1/dil)
Detectable HAI titer ≥ 10 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202	Percentage of participants with HAI titer ≥ 10 (1/dil)
GMTs of Abs against investigational pandemic flu H5 HA mRNA SD2 vaccine	Day 01, Day 22, Day 43, Day 112 and Day 202	Ab titer measured by seroneutralization (SN) test
Individual SN titer ratio	Day 22/Day 02, Day 43/Day 01, Day 112/Day 01 and Day 202/Day 01	GMR SN titers ratio
SN titer ≥ 20 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202	Percentage of participants with SN titer ≥ 20 (1/dil)
SN titer ≥ 40 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202	Percentage of participants with SN titer ≥ 40 (1/dil)
SN titer ≥ 80 (1/dil)	Day 01, Day 22, Day 43, Day 112 and Day 202	Percentage of participants with SN titer ≥ 80 (1/dil)
Detectable SN titer ≥ 10 (1/dil)	Day 01, Day 22, Day 43, Day 112, and Day 202	Percentage of participants with SN titer ≥ 10 (1/dil)
2-fold and 4-fold rise in SN titer	Day 22 and Day 43	Percentage of participants with fold increase in SN Ab titer \[post-vaccination / pre- vaccination\] ≥ 2 and ≥ 4 on D22 and D43

Trial Locations

Locations (13)

Velocity Clinical Research - San Diego- Site Number : 8400013; 🇺🇸 La Mesa, California, United States

Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400002; 🇺🇸 DeLand, Florida, United States

Accel Research Sites - Lakeland Clinical Research Unit- Site Number : 8400006; 🇺🇸 Lakeland, Florida, United States

Accel Research Sites Network - Largo- Site Number : 8400004; 🇺🇸 Largo, Florida, United States

Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400003; 🇺🇸 Decatur, Georgia, United States

QUEST Research Institute- Site Number : 8400014; 🇺🇸 Bingham Farms, Michigan, United States

Velocity Clinical Research - Norfolk- Site Number : 8400015; 🇺🇸 Norfolk, Nebraska, United States

Velocity Clinical Research - Omaha- Site Number : 8400012; 🇺🇸 Omaha, Nebraska, United States

Velocity Clinical Research - Springdale- Site Number : 8400010; 🇺🇸 Cincinnati, Ohio, United States

Coastal Carolina Research Center - North Charleston- Site Number : 8400001; 🇺🇸 North Charleston, South Carolina, United States

Olympus Clinical Research - Sugar Land- Site Number : 8400009; 🇺🇸 Sugar Land, Texas, United States

Velocity Clinical Research - Salt Lake City- Site Number : 8400011; 🇺🇸 West Jordan, Utah, United States

Charlottesville Medical Research- Site Number : 8400005; 🇺🇸 Charlottesville, Virginia, United States