Clinical trial NCT06686654: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Human Metapneumovirus Immunization
Respiratory Syncytial Virus Immunization
Keywords: hMPV
RSV
respiratory syncytial virus infection
human metapneumovirus infection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-11-13
Enrollment: 1530
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose-ranging, parallel, multi-center, placebo-controlled
Primary purpose: PREVENTION

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


Eligibility criteria: 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.

Primary outcomes:
measure: Presence of unsolicited immediate systemic adverse events (AEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Within 30 minutes after primary and booster vaccinations
measure: Presence of solicited injection site and systemic reactions (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Up to 7 days after primary and booster vaccinations
measure: Presence of unsolicited AEs (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Up to 28 days after primary and booster vaccinations
measure: Presence of medically attended AEs (MAAEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Up to 6 months after primary and booster vaccinations
measure: Presence of serious AEs (SAEs) and AEs of special interest (AESIs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Up to 6 months after primary and booster vaccinations
measure: Presence of related SAEs, related AESIs, and fatal SAEs (regardless of causality) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
timeFrame: Throughout the duration of the study (up to approximately 24 months)
measure: Presence of out-of-range biological test results (Stage 1)
timeFrame: Up to 7 days after primary vaccination
measure: hMPV A serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts
timeFrame: At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29)
measure: hMPV B serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts
timeFrame: At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29)
measure: RSV A serum nAb titers in Stage 1 Sentinel and Main Cohorts
timeFrame: At pre vaccination (D01) and 28 days post-primary vaccination (D29)
measure: RSV B serum nAb titers in Stage 1 Sentinel and Main Cohorts
timeFrame: At pre vaccination (D01) and 28 days post-primary vaccination (D29)
measure: hMPV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29)
measure: hMPV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29)
measure: RSV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29)
measure: RSV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV/RSV vaccine candidate (Day 29)
measure: hMPV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)
measure: hMPV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)
measure: RSV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)
measure: RSV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
timeFrame: At (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)
Secondary outcomes:
measure: hMPV serum anti-F immunoglobulin G (IgG) antibody (Ab) titers (Stage 1)
timeFrame: At pre-vaccination (D01) and 28 days (D29) post-primary vaccination
measure: RSV serum anti-F IgG Ab titers (Stage 1)
timeFrame: At pre-vaccination (D01) and 28 days (D29) post-primary vaccination
measure: hMPV A serum nAb titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
measure: hMPV B serum nAb titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
measure: hMPV A serum anti-F IgG Ab titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
measure: RSV A serum nAb titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
measure: RSV B serum nAb titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
measure: RSV serum anti-F IgG Ab titers (Stage 2 Expansion Cohort)
timeFrame: At pre-vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-primary vaccination
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Velocity Clinical Research, Phoenix- Site Number : 8400025
state: Arizona
city: Garden Grove
country: United States
facility: CenExel CNS-Garden Grove- Site Number : 8400017
state: California
city: Gardena
country: United States
facility: National Research Institute - Gardena- Site Number : 8400005
state: California
city: Huntington Park
country: United States
facility: National Research Institute - Huntington Park- Site Number : 8400014
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research - San Diego- Site Number : 8400008
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Research Los Angeles- Site Number : 8400013
state: California
city: Los Angeles
country: United States
facility: National Research Institute - Panorama City- Site Number : 8400012
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research - North Hollywood- Site Number : 8400018
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates- Site Number : 8400002
state: California
city: Englewood
country: United States
facility: Velocity Clinical Research - Denver- Site Number : 8400016
state: Colorado
city: Washington
country: United States
facility: Velocity Clinical Research - Washington DC- Site Number : 8400007
state: District of Columbia
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research - Hallandale Beach- Site Number : 8400022
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates - Miami - Sunset Drive- Site Number : 8400001
state: Florida
city: Meridian
country: United States
facility: Velocity Clinical Research - Meridian- Site Number : 8400003
state: Idaho
city: Overland Park
country: United States
facility: Velocity Clinical Research - Kansas City- Site Number : 8400015
state: Kansas
city: Rockville
country: United States
facility: Velocity Clinical Research - Rockville- Site Number : 8400011
state: Maryland
city: Lincoln
country: United States
facility: Velocity Clinical Research - Lincoln - Valley Road- Site Number : 8400023
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research - Omaha- Site Number : 8400006
state: Nebraska
city: Cincinnati
country: United States
facility: Velocity Clinical Research - Springdale- Site Number : 8400004
state: Ohio
city: Medford
country: United States
facility: Velocity Clinical Research - Medford- Site Number : 8400024
state: Oregon
city: Cedar Park
country: United States
facility: Velocity Clinical Research - Austin- Site Number : 8400020
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City- Site Number : 8400010
state: Utah
city: Hampton
country: United States
facility: Velocity Clinical Research - Hampton- Site Number : 8400026
state: Virginia
city: Seattle
country: United States
facility: Velocity Clinical Research - Seattle- Site Number : 8400019
state: Washington
Study officials:
References: