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

Phase 2Active Not RecruitingNCT06686654

Sanofi Pasteur, a Sanofi Company1,530 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,530

Eligibility

Sex: ALLMin age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Presence of unsolicited immediate systemic adverse events (AEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting immediate unsolicited systemic AEs

Time frame: Within 30 minutes after primary and booster vaccinations

Presence of solicited injection site and systemic reactions (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting solicited injection site and systemic reactions

Time frame: Up to 7 days after primary and booster vaccinations

Presence of unsolicited AEs (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting unsolicited AEs

Time frame: Up to 28 days after primary and booster vaccinations

Presence of medically attended AEs (MAAEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting MAAEs

Time frame: Up to 6 months after primary and booster vaccinations

Presence of serious AEs (SAEs) and AEs of special interest (AESIs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting SAEs and AESIs

Time frame: Up to 6 months after primary and booster vaccinations

Presence of related SAEs, related AESIs, and fatal SAEs (regardless of causality) (Stage 1 and Stage 2 Expansion and Booster Cohorts)

Number of participants reporting related SAEs, related AESIs, and fatal SAEs

Time frame: Throughout the duration of the study (up to approximately 24 months)

Presence of out-of-range biological test results (Stage 1)

Number of participants with out-of-range biological tests

Time frame: Up to 7 days after primary vaccination

Presence of out-of-range biological test results (Stage 2 Booster Cohort)

Number of participants with out-of-range biological tests

Time frame: Up to 7 days after booster vaccination

hMPV A serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts