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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 1
Recruiting
Conditions
Human Metapneumovirus Immunization
Respiratory Syncytial Virus Immunization
Interventions
Biological: Placebo
Biological: Investigational hMPV/RSV vaccine
Biological: Investigational RSV vaccine (monovalent)
Biological: Investigational hMPV vaccine (monovalent)
Biological: Licensed RSV Vaccine
Registration Number
NCT06686654
Lead Sponsor
Sanofi Pasteur, a Sanofi Company
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.

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 of the selected formulation administered 12 months after the primary vaccination in a subset of the study population.

The study duration is as follows:

-Six months each for the Sentinel and Main Cohorts; up to 12 months for the Expansion Cohort, and 12 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 selected formulation arm, and participants in the Licensed RSV vaccine arm will be followed for 12 months post-vaccination; the remainder of the participants will be followed for 8 months post-vaccination

* Stage 2 Booster Cohort: 1 IM injection 12 months post-primary vaccination. Participants will be followed for 12 months post-booster vaccination

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1510
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 11 Stage 1 Main CohortPlacebo1 IM injection of placebo
Group X Stage 2 Expansion CohortInvestigational hMPV/RSV vaccine1 IM injection of selected investigational hMPV/RSV vaccine formulation from Group 1-9 of Stage 1 Main Cohort
Group 12 Stage 2 Expansion CohortInvestigational RSV vaccine (monovalent)1 IM injection of investigational RSV monovalent vaccine
Group 13 Stage 2 Expansion CohortInvestigational hMPV vaccine (monovalent)1 IM injection of investigational hMPV monovalent vaccine
Group 14 Stage 2 Expansion CohortLicensed RSV Vaccine1 IM injection of licensed RSV vaccine
Group 9 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation I
Group 10 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation J
Group A Stage 1 Sentinel CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation A
Group B Stage 1 Sentinel CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation B
Group C Stage 1 Sentinel CohortPlacebo1 IM injection of placebo
Group 1 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation C
Group 2 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation D
Group 3 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation E
Group 4 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation F
Group 5 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation G
Group 6 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation A
Group 7 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation B
Group 8 Stage 1 Main CohortInvestigational hMPV/RSV vaccine1 IM injection of investigational hMPV/RSV vaccine formulation H
Group 15 Stage 2 Booster CohortInvestigational hMPV/RSV vaccine1 IM injection of selected investigational hMPV/RSV vaccine formulation from Group X of Expansion Cohort
Group 16 Stage 2 Booster CohortPlacebo1 IM injection of placebo
Primary Outcome Measures
NameTimeMethod
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

hMPV A serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main CohortsAt 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 CohortsAt 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 CohortsAt 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 CohortsAt 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 ChortAt (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)

nAb titers expressed as geometric mean titers (GMTs)

hMPV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion ChortAt (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)

nAb titers expressed as geometric mean titers (GMTs)

RSV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion ChortAt (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)

nAb titers expressed as geometric mean titers (GMTs)

RSV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion ChortAt (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)

nAb titers expressed as geometric mean titers (GMTs)

Secondary Outcome Measures
NameTimeMethod
RSV B serum nAb titers (Stage 2 Expansion Cohort)At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination

Ab titers expressed as geometric mean titers (GMTs)

RSV A serum nAb titers (Stage 2 Expansion Cohort)At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 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 (D01) and 28 days (D29) post-primary vaccination

Ab titers expressed as geometric mean titers (GMTs)

RSV serum anti-F IgG Ab titers (Stage 1)At pre-vaccination (D01) 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 (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination

Ab titers expressed as geometric mean titers (GMTs)

hMPV B serum nAb titers (Stage 2 Expansion Cohort)At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 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 (D01), 28 days (D29), and 3, 6, 9, and 12 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 (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination

Ab titers expressed as geometric mean titers (GMTs)

Trial Locations

Locations (24)

Velocity Clinical Research, Phoenix- Site Number : 8400025

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Phoenix, Arizona, United States

CenExel CNS-Garden Grove- Site Number : 8400017

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Garden Grove, California, United States

National Research Institute - Gardena- Site Number : 8400005

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Gardena, California, United States

National Research Institute - Huntington Park- Site Number : 8400014

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Huntington Park, California, United States

Velocity Clinical Research - San Diego- Site Number : 8400008

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La Mesa, California, United States

Velocity Clinical Research Los Angeles- Site Number : 8400013

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Los Angeles, California, United States

National Research Institute - Panorama City- Site Number : 8400012

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Los Angeles, California, United States

Providence Clinical Research - North Hollywood- Site Number : 8400018

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North Hollywood, California, United States

Peninsula Research Associates- Site Number : 8400002

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Rolling Hills Estates, California, United States

Velocity Clinical Research - Denver- Site Number : 8400016

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Englewood, Colorado, United States

Velocity Clinical Research - Washington DC- Site Number : 8400007

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Washington, District of Columbia, United States

Velocity Clinical Research - Hallandale Beach- Site Number : 8400022

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Hallandale Beach, Florida, United States

Suncoast Research Associates - Miami - Sunset Drive- Site Number : 8400001

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Miami, Florida, United States

Velocity Clinical Research - Meridian- Site Number : 8400003

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Meridian, Idaho, United States

Velocity Clinical Research - Kansas City- Site Number : 8400015

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Overland Park, Kansas, United States

Velocity Clinical Research - Rockville- Site Number : 8400011

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Rockville, Maryland, United States

Velocity Clinical Research - Lincoln - Valley Road- Site Number : 8400023

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Lincoln, Nebraska, United States

Velocity Clinical Research - Omaha- Site Number : 8400006

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Omaha, Nebraska, United States

Velocity Clinical Research - Springdale- Site Number : 8400004

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Cincinnati, Ohio, United States

Velocity Clinical Research - Medford- Site Number : 8400024

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Medford, Oregon, United States

Velocity Clinical Research - Austin- Site Number : 8400020

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Cedar Park, Texas, United States

Velocity Clinical Research - Salt Lake City- Site Number : 8400010

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West Jordan, Utah, United States

Velocity Clinical Research - Hampton- Site Number : 8400026

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Hampton, Virginia, United States

Velocity Clinical Research - Seattle- Site Number : 8400019

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Seattle, Washington, United States

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