Study to Assess Safety and Immunogenicity of an Egg-based H5N8 Influenza Vaccine at Multiple Dose Levels Adjuvanted With Matrix-M in Healthy Participants 18 Years of Age and Above.

A Phase 1/2, Parallel, Observer-blind Study to Assess the Safety and Immunogenicity of an Egg-based H5N8 Influenza Vaccine at Multiple Dose Levels Adjuvanted With Matrix-M in Healthy Participants 18 Years of Age and Above.

The study aims to evaluate an egg-based H5N8 influenza vaccine up to 3 dose levels (low, medium, and high dose) given with or without adjuvant to see if the adjuvant improves vaccine effectiveness.

The study will enroll healthy adults aged 18 years and over. Participants will receive 2 injections in their arm of either one of the 3 dose levels of the study vaccine (low, medium, or high dose) with the adjuvant or the unadjuvanted vaccine (high dose).

Study duration per participant: approximately 14 months (including screening visit).

Study Overview

• Status: Not yet recruiting
• Conditions: Influenza; Healthy Volunteers
• Intervention / Treatment: Biological: Flu H5 egg pandemic low dose vaccine, with adjuvant; Biological: Flu H5 Egg Pandemic medium dose vaccine, with adjuvant; Biological: Flu H5 Egg Pandemic high dose vaccine, with adjuvant; Biological: Flu H5 Egg Pandemic high dose vaccine, without adjuvant

• Study Type: Interventional
• Enrollment (Estimated): 640
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years or above on the day of inclusion
• Participants who are healthy as determined by medical evaluation including medical history
• Not pregnant/breastfeeding; non-childbearing potential or uses effective contraception/abstinence from ≥4 weeks before the first study intervention dose to ≥8 weeks after the last dose
• Informed consent form has been signed and dated
• Able to attend all scheduled visits and to comply with all study procedures
• Covered by health insurance, if required by local regulations

Exclusion Criteria:

• Known or suspected immunodeficiency; immunosuppressive therapy in past 6 months; or long-term systemic corticosteroid (eg, prednisone for more than 2 weeks in the past 3 months)
• Known hepatitis B or hepatitis C infection (based on medical history)
• Known personal or family history of previous episodes of Guillan-Barré syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
• Known systemic hypersensitivity to any of the study intervention components or history of life-threatening reaction to the study interventions or products with same substances
• Self-reported thrombocytopenia contraindicating intramuscular (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
• History of A/H5 infection prior to the study participation
• Moderate or severe acute illness/infection (per investigator judgment)/fever (≥ 38.0°C [≥ 100.4°F]) on study intervention day. Include participant only after the condition or fever has resolved
• Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
• Any vaccine given 4 weeks before first study intervention or any planned vaccination to be given prior to Day 43 (ie, approximately 21 days after the second study intervention)
• Previous vaccination against A(H5) with an investigational or marketed vaccine. This includes, but is not limited to, influenza subtypes A(H5N1), A(H5N8), and A(H5N6)
• Has received a blood transfusion or blood-derived products, including immunoglobulins in the past 3 months
• Participation in another clinical study for a vaccine, drug, medical device, or medical procedure within 4 weeks before enrollment or planned participation during the present study period
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Is an investigator, investigator/study center employee, or immediate family member (parent, spouse, natural/adopted child) of the investigator/employee with direct involvement in the study
• Any screening safety laboratory parameters out of normal ranges and assessed as > Grade 2

The above information is not intended to contain all considerations relevant to a participant'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: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Flu H5 egg pandemic low dose vaccine, with adjuvant; Participants receive 2 intramuscular injections of flu H5 egg pandemic low dose vaccine, with adjuvant	Biological: Flu H5 egg pandemic low dose vaccine, with adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
Experimental: Group 2: Flu H5 Egg Pandemic medium dose vaccine, with adjuvant; Participants receive 2 intramuscular injections of flu H5 egg pandemic medium dose vaccine, with adjuvant	Biological: Flu H5 Egg Pandemic medium dose vaccine, with adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
Experimental: Group 3: Flu H5 Egg Pandemic high dose vaccine, with adjuvant; Participants receive 2 intramuscular injections of flu H5 egg pandemic high dose vaccine, with adjuvant	Biological: Flu H5 Egg Pandemic high dose vaccine, with adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
Experimental: Group 4: Flu H5 Egg Pandemic high dose vaccine, without adjuvant; Participants receive 2 intramuscular injections of flu H5 egg pandemic high dose vaccine, without adjuvant	Biological: Flu H5 Egg Pandemic high dose vaccine, without adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immediate Adverse Events (AEs)	Immediate adverse events are medically relevant unsolicited systemic adverse events reported in the 30 minutes after vaccination	Within 30 minutes after each vaccination
Number of participants experiencing solicited administration site reactions (pre-listed in the participant diary and case report form [CRF])	A solicited reaction is an adverse reaction (sign or symptom) observed and reported under the conditions pre-listed (for example: injection site pain or headache). Solicited administration site reactions are reactions at and around the injection/administration site	Within 8 days of each vaccination, including the day of vaccination
Number of participants experiencing solicited systemic reactions (pre-listed in the participant diary and CRF)	All solicited reactions that are not solicited injection or administration site reactions	Within 8 days of each vaccination, including the day of vaccination
Number of participants experiencing unsolicited AEs	Unsolicited AE: an observed AE that does not fulfill the conditions of solicited reactions	Within 21 days after the first vaccination, including the day of the first vaccination, and within 28 days after the second vaccination, including the day of the second vaccination
Number of participants experiencing Medically Attended Adverse Events (MAAEs)	MAAEs are collected throughout the study	From Day 01 until the end of the study, approximately 14 months
Number of participants experiencing Adverse Events of Special Interest (AESIs)	AESIs are collected throughout the study	From Day 01 until the end of the study, approximately 14 months
Number of participants experiencing Serious Adverse Events (SAEs)	SAEs are collected throughout the study	From Day 01 until the end of the study, approximately 14 months
Number of participants experiencing out-of-range biological test results (including shift from baseline values)	Safety laboratory assessments will include clinical chemistry and hematology	Up to 8 days after each vaccination
Number of participants experiencing AEs leading to discontinuation	AEs leading to discontinuation are collected throughout the study	From Day 01 until the end of the study, approximately 14 months
Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer	Influenza vaccine antibody titers are measured by HAI assay	Day 01 and Day 43
Number of participants with HAI Ab titer ≥ 40 (1 dilution [dil]; ie, seroprotection)	Influenza vaccine antibody titers are measured by HAI assay	Day 43
Number of participants with seroconversion	Seroconversion is defined as HAI Ab titer < 10 (1/dil) on Day 01 and post-injection titer ≥ 40 (1/dil) on Day 43; or defined as HAI Ab titer ≥ 10 (1/dil) on Day 01 and a ≥ 4-fold increase in titer (1/dil) on Day 43	Day 01 and Day 43
Geometric mean titer ratio of individual HAI Ab titer ratio Day 43/Day 01	Influenza vaccine antibody titers are measured by HAI assay	Day 01 and Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer obtained on Day 01, Day 22, Day 43, Day 202	Influenza vaccine antibody titers are measured by HAI assay	Day 01, Day 22, Day 43, Day 202
Geometric mean titer ratio of individual HAI Ab titer ratios Day 22/Day 01, Day 43/Day 01, Day 202/Day 43	Individual HAI Ab titer ratios are calculated for the following time points: Day 22/Day 01, Day 43/Day 01 and Day 202/Day 43	Day 01, Day 22, Day 43, Day 202
Number of participants with individual HAI Ab titer ≥ 40 (1/dil) on Day 01, Day 22, Day 43, Day 202	Influenza vaccine antibody titers are measured by HAI assay	Day 01, Day 22, Day 43, Day 202
Number of participants with seroconversion on Day 22 compared to Day 01 (baseline)	Seroconversion is defined as titer < 10 (1/dil) on Day 01 and post-injection titer ≥ 40 (1/dil) on Day 22; or defined as titer ≥ 10 (1/dil) on Day 01 and a ≥ 4 fold increase in titer (1/dil) on Day 22	Day 01, Day 22
Number of participants with detectable HAI Ab titer	Detectable HAI Ab titer: a titer ≥ 10 (1/dil)	Day 01, Day 22, Day 43, Day 202
Geometric mean titer of neutralization (NT) Ab titer	Influenza vaccine antibody titers are measured by serum neutralization (SN) assay	Day 01, Day 22, Day 43, Day 202
Geometric mean titer ratio of individual NT Ab titer ratio	Individual NT Ab titer ratios are calculated for the following time points: Day 22/Day 01, Day 43/Day 01 and Day 202/Day 43	Day 01, Day 22, Day 43, Day 202
Number of participants with NT Ab titer ≥ 20 (1/dil)	NT Ab titer ≥ 20 (1/dil) on Day 43; compared to Day 01 and Day 202	Day 01, Day 43, Day 202
Number of participants with NT Ab titer ≥ 40 (1/dil)	NT Ab titer ≥ 40 (1/dil) on Day 43; compared to Day 01 and Day 202	Day 01, Day 43, Day 202
Number of participants with NT Ab titer ≥ 80 (1/dil)	NT Ab titer ≥ 80 (1/dil) on Day 43; compared to Day 01 and Day 202	Day 01, Day 43, Day 202
Geometric mean fold-rise of fold increase in NT Ab titer [post/pre] ≥ 2 and ≥ 4	Influenza vaccine antibody titers are measured by serum neutralization (SN) assay	Day 43
Number of participants with detectable NT Ab titer	Detectable NT Ab titer: a titer ≥ 10 (1/dil) on Day 01, Day 22, Day 43, Day 202	Day 01, Day 22, Day 43, Day 202

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): February 22, 2028
• Study Completion (Estimated): February 22, 2028

Study Registration Dates

• First Submitted: July 31, 2026
• First Submitted That Met QC Criteria: August 19, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 19, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Vaccines
• Other Study ID Numbers: VBX21138; U1111-1325-2670 (Registry Identifier: 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