Study of a Human Metapneumovirus/Respiratory Syncytial Virus mRNA Vaccine Candidate Encapsulated in a Lipid Nanoparticle-based Formulation in Adults Aged 60 Years and Older

A Phase 1/2, Randomized, Observer-blind, Placebo-controlled Multi-arm Study to Evaluate the Safety and Immunogenicity of an hMPV/RSV mRNA Vaccine Candidate in Adult Participants Aged 60 Years and Older

The aim of this study is to evaluate the safety and immunogenicity of a human metapneumovirus (hMPV) / respiratory syncytial virus (RSV) mRNA vaccine candidate encapsulated in a lipid nanoparticle (LNP) based formulation (hereafter referred to as hMPV/RSV vaccine) for the prevention of lower respiratory tract disease (LRTD) caused by hMPV and/or RSV among adults aged 60 years and older.

The study will also evaluate the safety and immunogenicity of a booster vaccination using a bivalent hMPV/RSV mRNA vaccine candidate (hereafter referred to as RSV+hMPV mRNA vaccine candidate).

Overall, the study is designed to address the following goals:

• Assess the safety profile of the candidate formulations.
• Describe the immunogenicity profile of the candidate formulations.
• Select the vaccine formulations (dose) for future development.
• Assess the safety and immunogenicity of a booster vaccination with the RSV + hMPV mRNA vaccine candidate administered 12 months after primary vaccination with a licensed RSV vaccine.

The study duration is as follows:

-Six months each for the Sentinel and Main Cohorts; up to 12 months for the Expansion Cohort, and 6 additional months for the Booster Cohort

Treatment duration:

• Stage 1 Sentinel Cohort: 1 intra-muscular (IM) injection. Participants will be followed for 6 months post vaccination
• Stage 1 Main Cohort: 1 IM injection. Participants will be followed for 6 months post vaccination
• Stage 2 Expansion Cohort: 1 IM injection. Participants in the licensed RSV vaccine arm will be followed for 12 months post-vaccination; the remainder of the participants will be followed up to 8 months post-vaccination
• Stage 2 Booster Cohort: 1 IM injection 12 months post-primary vaccination. Participants will be followed for 6 months post-booster vaccination

Inclusion Criteria:

• Aged 60 years or older on the day of inclusion
• A female participant is eligible to participate if she is not pregnant or breastfeeding and 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

Exclusion Criteria:

• Any screening laboratory parameter with laboratory abnormality > Grade 1 deemed clinically significant by the investigator
• 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). Of note, persons living with stable human immunodeficiency virus (HIV) are not excluded
• 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
• History of RSV and/or hMPV-associated illness, diagnosed serologically or microbiologically in the last 12 months
• Previous history of myocarditis, pericarditis, and/or myopericarditis
• Screening electrocardiogram that is consistent with possible myocarditis, pericarditis, and/or myopericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
• Laboratory-confirmed 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
• Receipt of any vaccine other than mRNA vaccine in the 28 days preceding any study intervention administration or planned receipt of any vaccine other than mRNA vaccine in the 28 days following any study intervention administration
• Receipt of any mRNA vaccine in the 60 days preceding any study intervention administration or planned receipt of any mRNA vaccine in the 60 days following any study intervention administration
• Previous vaccination against RSV and/or hMPV (with a licensed or investigational vaccine either as a monovalent vaccine or any combination of the antigens)
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months

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