Clinical trial NCT05639894: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Syncytial Virus Immunization
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-12-07
Enrollment: 865
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sequential (Phase I)/ parallel (Phase IIa)
Primary purpose: PREVENTION

Brief summary: Brief Summary of Stage 1:

The purpose Stage 1 (Phase I/IIa) is 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 are to assess the safety and immunogenicity profiles across the dose-level groups (low, medium, and high doses) with 2 LNPs. This stage will evaluate 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 also incorporates a Stage 2 (Phase IIa, dose-ranging design) that includes 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 will be randomly assigned in a 1:1:1 ratio to receive a single IM administration of RSV vaccine candidate doses, or placebo. Multiple safety analyses will be performed, minimally at D07 and D28. Additional analyses may be performed as data are available.

Detailed description: Stage 1:

The duration of each participant's participation is 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 will be followed for 12 months post-vaccination.
* Main Cohort: 1 IM injection. Participants will be followed for 12 months post-vaccination.
* Booster Cohort: 1 IM injection 12 months after the primary vaccination. Participants will be followed for 12 months after administration of the booster dose.

Stage 2:

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

Treatment Duration:

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

Eligibility criteria: 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 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 OR
  * Is 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 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.
* Able to attend all scheduled visits and to comply with all study procedures
* Informed consent form has 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, is 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 any vaccine other than mRNA vaccine in the 4 weeks preceding any study intervention administration or planned receipt of any vaccine other than mRNA vaccine in the 4 weeks 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 with an investigational vaccine
* 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 is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: Presence of unsolicited systemic adverse events (AEs)
timeFrame: Within 30 minutes after vaccination
measure: Presence of solicited injection site or systemic reactions
timeFrame: Within 7 days after vaccination
measure: Presence of unsolicited AEs
timeFrame: Within 28 days after vaccination
measure: Presence of medically attended adverse events (MAAEs)
timeFrame: Within 28 days after vaccination
measure: Presence of serious adverse events (SAEs)
timeFrame: Month 12
measure: Presence of adverse events of special interest (AESIs)
timeFrame: Month 12
measure: Presence of out-of-range biological test results
timeFrame: Within 7 days after vaccination
measure: Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers pre-vaccination at Day 1
timeFrame: Day 1
measure: Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29
timeFrame: Day 29
Secondary outcomes:
measure: Presence of immediate unsolicited systemic AEs (Stage 1)
timeFrame: Within 30 minutes after vaccination
measure: Presence of solicited injection site or systemic reactions post-booster vaccination (Stage 1)
timeFrame: Within 7 days after vaccination
measure: Presence of unsolicited AEs post-booster vaccination (Stage 1)
timeFrame: Within 28 days after vaccination
measure: Presence of MAAEs (Stage 1)
timeFrame: Within 28 days after vaccination
measure: Presence of serious adverse events (SAEs) post-booster vaccination (Stage 1)
timeFrame: Throughout the booster study, approximately 12 months
measure: Presence of adverse events of special interest post-booster vaccination (Stage 1)
timeFrame: Throughout the booster study, approximately 12 months
measure: Presence of out-of-range biological test results post-booster vaccination (Stage 1)
timeFrame: Within 7 days after vaccination
measure: RSV-A serum nAb titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) (Stage 1)
timeFrame: Day 1, Day 29, Month 3, Month 6 and Month 12
measure: GMTs of serum anti-F immunoglobulin G (IgG) antibody (Ab) titers post-primary vaccination (Stage 1)
timeFrame: Day 1, Day 29, Month 3, Month 6 and Month 12
measure: GMTs of RSV-A serum nAb post-booster vaccination (Stage 1)
timeFrame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster
measure: GMTs of serum anti-F IgG Ab titers post-booster vaccination (Stage 1)
timeFrame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster
measure: GMTs of serum anti-F IgG Ab titers pre-vaccination (Stage 2)
timeFrame: Day 1
measure: GMTs of serum anti-F IgG Ab titers post-vaccination (Stage 2)
timeFrame: Day 29
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Optimal Research Alabama Site Number : 8400032
state: Alabama
city: Mesa
country: United States
facility: Aventiv Research Mesa Site Number : 8400020
state: Arizona
city: Peoria
country: United States
facility: CVS Health - Peoria Site Number : 8400042
state: Arizona
city: Phoenix
country: United States
facility: CVS Health - Phoenix Site Number : 8400041
state: Arizona
city: La Mesa
country: United States
facility: Velocity Clinical Research - San Diego - ERN - PPDS Site Number : 8400010
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates Site Number : 8400013
state: California
city: Thousand Oaks
country: United States
facility: CVS Health - Thousand Oaks Site Number : 8400043
state: California
city: Hollywood
country: United States
facility: Cenexel Research Centers of America Site Number : 8400024
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates, LLC Site Number : 8400003
state: Florida
city: Rincon
country: United States
facility: Centricity Research - Georgia Site Number : 8400009
state: Georgia
city: Peoria
country: United States
facility: AES Peoria Site Number : 8400030
state: Illinois
city: River Forest
country: United States
facility: DM Clinical Research - Chicago Site Number : 8400027
state: Illinois
city: Lincoln
country: United States
facility: Be Well Clinical Studies Site Number : 8400036
state: Nebraska
city: Cincinnati
country: United States
facility: Velocity Clinical Research Site Number : 8400019
state: Ohio
city: Cleveland
country: United States
facility: Velocity Clinical Research Site Number : 8400017
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Columbus Site Number : 8400007
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman Site Number : 8400023
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research, Medford Site Number : 8400014
state: Oregon
city: East Greenwich
country: United States
facility: Velocity Clinical Research - Providence Site Number : 8400006
state: Rhode Island
city: North Charleston
country: United States
facility: Coastal Carolina Research Center Site Number : 8400015
state: South Carolina
city: Houston
country: United States
facility: DM Clinical Research - CyFair Site Number : 8400025
state: Texas
city: Round Rock
country: United States
facility: Be Well Clinical Studies -Round Rock Site Number : 8400038
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research-San Antonio Site Number : 8400039
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic Site Number : 8400026
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research Site Number : 8400018
state: Utah
city: Botany
country: Australia
facility: Investigational Site Number : 0360003
state: New South Wales
city: Camberwell
country: Australia
facility: Investigational Site Number : 0360002
state: Victoria
city: Southport
country: Australia
facility: Investigational Site Number : 0360001
city: Carolina
country: Puerto Rico
facility: Investigational Site Number : 6300004
city: Guayama
country: Puerto Rico
facility: Investigational Site Number : 6300003
city: Guaynabo
country: Puerto Rico
facility: Investigational Site Number : 6300005
city: San Juan
country: Puerto Rico
facility: Investigational Site Number : 6300001
city: San Juan
country: Puerto Rico
facility: Investigational Site Number : 6300002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: