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
Overview
- Phase
- Phase 1
- Intervention
- RSV vaccine candiate formulation 1
- Conditions
- Respiratory Syncytial Virus Immunization
- Sponsor
- Sanofi Pasteur, a Sanofi Company
- Enrollment
- 865
- Locations
- 33
- Primary Endpoint
- Presence of unsolicited systemic adverse events (AEs)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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
Investigators
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
Arms & Interventions
Group 1: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
Intervention: RSV vaccine candiate formulation 1
Group 2: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
Intervention: RSV vaccine candidate formulation 2
Group 3: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
Intervention: RSV vaccine candiate formulation 1
Group 4: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
Intervention: RSV vaccine candidate formulation 2
Group 5: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose C) via intramuscular injection
Intervention: RSV vaccine candiate formulation 1
Group 6: Sentinel and Main Cohorts (Stage 1)
1 injection of RSV vaccine candidate (Dose C) via intramuscular injection
Intervention: RSV vaccine candidate formulation 2
Group 7: Main, Sentinel and Booster Cohorts (Stage 1)
1 injection of placebo via intramuscular injection
Intervention: Placebo
Group 0: Phase IIa/Dose-ranging (Stage 2)
1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
Intervention: RSV vaccine candiate formulation 1
Group 1: Phase IIa/Dose-ranging (Stage 2)
1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
Intervention: RSV vaccine candidate formulation 2
Group 2: Phase 11a/Dose-ranging (Stage 2)
1 injection of placebo via intramuscular injection
Intervention: Placebo
Outcomes
Primary Outcomes
Presence of unsolicited systemic adverse events (AEs)
Time Frame: Within 30 minutes after vaccination
Number of participants experienciing unsolicited systemic adverse events
Presence of solicited injection site or systemic reactions
Time Frame: Within 7 days after vaccination
Number of participants reporting: * injection site reactions: pain, erythema and swelling * systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
Presence of unsolicited AEs
Time Frame: Within 28 days after vaccination
Number of participants experiencing unsolicited AEs
Presence of medically attended adverse events (MAAEs)
Time Frame: Within 28 days after vaccination
Number of participants experiencing MAAEs
Presence of serious adverse events (SAEs)
Time Frame: Month 12
Number of participants experiencing SAEs
Presence of adverse events of special interest (AESIs)
Time Frame: Month 12
Number of participants experiencing AESIs
Presence of out-of-range biological test results
Time Frame: Within 7 days after vaccination
Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers pre-vaccination at Day 1
Time Frame: Day 1
Nab titers pre-vaccination
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29
Time Frame: Day 29
Nab titers post-vaccination
Secondary Outcomes
- Presence of immediate unsolicited systemic AEs (Stage 1)(Within 30 minutes after vaccination)
- Presence of solicited injection site or systemic reactions post-booster vaccination (Stage 1)(Within 7 days after vaccination)
- Presence of unsolicited AEs post-booster vaccination (Stage 1)(Within 28 days after vaccination)
- Presence of MAAEs (Stage 1)(Within 28 days after vaccination)
- Presence of serious adverse events (SAEs) post-booster vaccination (Stage 1)(Throughout the booster study, approximately 12 months)
- Presence of adverse events of special interest post-booster vaccination (Stage 1)(Throughout the booster study, approximately 12 months)
- Presence of out-of-range biological test results post-booster vaccination (Stage 1)(Within 7 days after vaccination)
- RSV-A serum nAb titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12)
- GMTs of serum anti-F immunoglobulin G (IgG) antibody (Ab) titers post-primary vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12)
- GMTs of serum anti-F IgG Ab titers pre-vaccination (Stage 2)(Day 1)
- GMTs of serum anti-F IgG Ab titers post-vaccination (Stage 2)(Day 29)
- GMTs of serum anti-F IgG Ab titers post-booster vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster)
- GMTs of RSV-A serum nAb post-booster vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster)