Clinical trial NCT06907511: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pandemic Influenza Immunization
Healthy Volunteers
Keywords: Pandemic Flu H5 Vaccination
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2025-04-02
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Presence of immediate adverse events (AEs)
timeFrame: Within 30 minutes after each/any injection
measure: Presence of solicited injection site reactions
timeFrame: Through 7 days after each/any injection
measure: Presence of solicited systemic reactions
timeFrame: Through 7 days after each/any injection
measure: Presence of unsolicited AEs
timeFrame: Through 21 days after the first injection through 28 days after the second injection
measure: Presence of medically attended adverse events (MAAEs)
timeFrame: Through 180 days after the last injection
measure: Presence of adverse events of special interest (AESIs)
timeFrame: Throughout the study, approximately 13 months
measure: Presence of serious adverse events (SAEs)
timeFrame: Throughout the study, approximately 13 months
measure: Presence of out-of-range biological test results (including shift from baseline values)
timeFrame: Through a maximum of 8 days after each injection
Secondary outcomes:
measure: Geometric mean titers (GMTs) of antibodies (Abs) against investigational pandemic flu H5 HA mRNA SD2 vaccine
timeFrame: Day 01, Day 22, Day 43, Day 112 and Day 202
measure: Individual HA titer ratio
timeFrame: Day22/Day01, Day43/Day01, Day112/Day01, and Day202/Day01
measure: Seroconversion HAI Titer
timeFrame: Day 01, Day 22 and Day 43
measure: HAI titer ≥ 40 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112, and Day 202
measure: Detectable HAI titer ≥ 10 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112, and Day 202
measure: GMTs of Abs against investigational pandemic flu H5 HA mRNA SD2 vaccine
timeFrame: Day 01, Day 22, Day 43, Day 112 and Day 202
measure: Individual SN titer ratio
timeFrame: Day 22/Day 02, Day 43/Day 01, Day 112/Day 01 and Day 202/Day 01
measure: SN titer ≥ 20 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112 and Day 202
measure: SN titer ≥ 40 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112 and Day 202
measure: SN titer ≥ 80 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112 and Day 202
measure: Detectable SN titer ≥ 10 (1/dil)
timeFrame: Day 01, Day 22, Day 43, Day 112, and Day 202
measure: 2-fold and 4-fold rise in SN titer
timeFrame: Day 22 and Day 43
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Velocity Clinical Research - San Diego- Site Number : 8400013
state: California
city: DeLand
country: United States
facility: Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400002
state: Florida
city: Lakeland
country: United States
facility: Accel Research Sites - Lakeland Clinical Research Unit- Site Number : 8400006
state: Florida
city: Largo
country: United States
facility: Accel Research Sites Network - Largo- Site Number : 8400004
state: Florida
city: Decatur
country: United States
facility: Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400003
state: Georgia
city: Bingham Farms
country: United States
facility: QUEST Research Institute- Site Number : 8400014
state: Michigan
city: Norfolk
country: United States
facility: Velocity Clinical Research - Norfolk- Site Number : 8400015
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research - Omaha- Site Number : 8400012
state: Nebraska
city: Cincinnati
country: United States
facility: Velocity Clinical Research - Springdale- Site Number : 8400010
state: Ohio
city: North Charleston
country: United States
facility: Coastal Carolina Research Center - North Charleston- Site Number : 8400001
state: South Carolina
city: Sugar Land
country: United States
facility: Olympus Clinical Research - Sugar Land- Site Number : 8400009
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City- Site Number : 8400011
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research- Site Number : 8400005
state: Virginia
Study officials:
References: