Study of a Respiratory Syncytial Virus Candidate Encapsulated in a Lipid Nanoparticle Based Formulation in Adults Aged 18 to 50 Years and 60 Years and Older

A Phase I/IIa, Randomized, Placebo-controlled Multi-arm Dose-finding Study to Evaluate the Safety and Immunogenicity of a RSV Vaccine Candidate in Adult Participants 18 to 50 Years of Age in Phase I, and 60 Years and Older in Phase IIa

Brief Summary of Stage 1:

The purpose of Stage 1 (Phase I/IIa) was to assess the safety and immunogenicity of a single intramuscular (IM) injection of 3 dose-levels of an Respiratory Syncytial Virus (RSV) vaccine candidate formulated with 2 different lipid nanoparticles (LNPs) in healthy adult participants aged between 18 to 50 years, and 60 years and older. The primary objectives of this stage were to assess the safety and immunogenicity profiles across the dose-level groups (low, medium, and high doses) with 2 LNPs. This stage evaluated the safety and immunogenicity of a booster vaccination administered 12 months after the primary vaccination in a subset of the study population.

Brief Summary of Stage 2:

The study also incorporated a Stage 2 (Phase IIa, dose-ranging design) that included adults aged 60 years and older to assess the safety and immunogenicity of different doses of RSV vaccine encapsulated in one of the LNPs. In the Phase IIa dose-ranging stage, eligible participants were randomly assigned in a 1:1:1 ratio to receive a single IM administration of RSV vaccine candidate doses, or placebo. Multiple safety analyses were performed, minimally at D07 and D28.

Stage 1:

The duration of each participant's participation was 12 months for the Sentinel and Main Cohorts, 24 months overall for the subset of participants enrolled in the Booster Cohort.

Treatment Duration:

• Sentinel Cohort: 1 intra-muscular (IM) injection. Participants were followed for 12 months post-vaccination.
• Main Cohort: 1 IM injection. Participants were followed for 12 months post-vaccination.
• Booster Cohort: 1 IM injection 12 months after the primary vaccination. Participants were followed for 12 months after administration of the booster dose.

Stage 2:

The duration of each participant's participation was approximately 6 months.

Treatment Duration:

1 IM injection. Participants were followed for approximately 6 months post vaccination

Inclusion Criteria:

• Sentinel Cohort Stage 1: Aged 18 to 50 years on the day of inclusion
• Main Cohort Stage 1 and Stage 2: Aged 60 years or older on the day of inclusion

Stage 1 and Stage 2:

• Sentinel Cohort: A female participant was eligible to participate if she was not pregnant or breastfeeding and:

  • Was of non-childbearing potential. To be considered of non-childbearing potential, a female must have been postmenopausal for at least 1 year or surgically sterile OR
  • Was of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.

• Main and Booster Cohorts: A female participant was eligible to participate if she was not pregnant or breastfeeding and:

  • Was of non-childbearing potential. To be considered of non-childbearing potential, a female must have been postmenopausal for at least 1 year or surgically sterile.

• Able to attend all scheduled visits and to comply with all study procedures

• Informed consent form was been signed and dated

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 mRNA COVID-19 vaccine
• History of RSV-associated illness, diagnosed clinically, serologically, or microbiologically in the last 12 months
• Previous history of myocarditis, pericarditis, and/or myopericarditis
• Thrombocytopenia or bleeding disorder, contraindicating IM injection based on investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion
• Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
• Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Self-reported or documented human immunodeficiency virus (HIV) detected by any FDA-approved/validated test, hepatitis B virus surface antigen (HBsAg), hepatits B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs), or positive SARS-CoV-2 RT-PCR or antigen test
• Identified as an investigator or employee of the investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the investigator or employee with direct involvement in the proposed study

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