Human Metapneumovirus Immunization, Respiratory Syncytial Virus Immunization
Conditions
Keywords
hMPV, RSV, respiratory syncytial virus infection, human metapneumovirus infection
Brief summary
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
Interventions
BIOLOGICALInvestigational hMPV/RSV vaccine
Investigational hMPV/RSV vaccine administered intramuscularly
BIOLOGICALInvestigational hMPV vaccine (monovalent)
Investigational hMPV vaccine (monovalent) administered intramuscularly
BIOLOGICALInvestigational RSV vaccine (monovalent)
Investigational RSV vaccine (monovalent) administered intramuscularly
BIOLOGICALLicensed RSV Vaccine
Licensed RSV vaccine administered intramuscularly
BIOLOGICALPlacebo
Placebo administered intramuscularly
BIOLOGICALInvestigational RSV+hMPV vaccine
Investigational RSV+hMPV vaccine administered intramuscularly
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Stage 1 Sentinel and Main Cohorts: observer-blind; for safety evaluation purposes, the Sponsor Safety Management Team (SMT) will be unblinded for the Sentinel Cohort (including early safety data review \[ESDR\]) and will be blinded for the Main Cohort. Stage 2 Expansion Cohort: observer-blind until all participants complete the Month 6 visit, then open-label Stage 2 Booster Cohort: open-label
Intervention model description
Dose-ranging, parallel, multi-center, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort | At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| Presence of out-of-range biological test results (Stage 2 Booster Cohort) | Up to 7 days after booster vaccination | Number of participants with out-of-range biological tests |
| hMPV A serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts | At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| hMPV B serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts | At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| RSV A serum nAb titers in Stage 1 Sentinel and Main Cohorts | At pre vaccination (D01) and 28 days post-primary vaccination (D29) | nAb titers expressed as geometric mean titers (GMTs) |
| RSV B serum nAb titers in Stage 1 Sentinel and Main Cohorts | At pre vaccination (D01) and 28 days post-primary vaccination (D29) | nAb titers expressed as geometric mean titers (GMTs) |
| hMPV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort | At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| hMPV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort | At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| RSV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort | At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29) | nAb titers expressed as geometric mean titers (GMTs) |
| Presence of unsolicited immediate systemic adverse events (AEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Within 30 minutes after primary and booster vaccinations | Number of participants reporting immediate unsolicited systemic AEs |
| Presence of solicited injection site and systemic reactions (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Up to 7 days after primary and booster vaccinations | Number of participants reporting solicited injection site and systemic reactions |
| Presence of unsolicited AEs (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Up to 28 days after primary and booster vaccinations | Number of participants reporting unsolicited AEs |
| Presence of medically attended AEs (MAAEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Up to 6 months after primary and booster vaccinations | Number of participants reporting MAAEs |
| Presence of serious AEs (SAEs) and AEs of special interest (AESIs) (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Up to 6 months after primary and booster vaccinations | Number of participants reporting SAEs and AESIs |
| Presence of related SAEs, related AESIs, and fatal SAEs (regardless of causality) (Stage 1 and Stage 2 Expansion and Booster Cohorts) | Throughout the duration of the study (up to approximately 24 months) | Number of participants reporting related SAEs, related AESIs, and fatal SAEs |
| Presence of out-of-range biological test results (Stage 1) | Up to 7 days after primary vaccination | Number of participants with out-of-range biological tests |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV serum anti-F IgG Ab titers (Stage 1) | At pre-vaccination (Day 01) and 28 days (D29) post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| hMPV A serum nAb titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| hMPV B serum nAb titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| hMPV A serum anti-F IgG Ab titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| RSV A serum nAb titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| RSV B serum nAb titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| RSV serum anti-F IgG Ab titers (Stage 2 Expansion Cohort) | At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
| hMPV serum anti-F immunoglobulin G (IgG) antibody (Ab) titers (Stage 1) | At pre-vaccination (Day 01) and 28 days (D29) post-primary vaccination | Ab titers expressed as geometric mean titers (GMTs) |
Countries
United States
Outcome results
None listed