Study of a Respiratory Syncytial Virus/Human Metapneumovirus Vaccine Candidate

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of a single intramuscular (IM) injection of different doses of an respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccine candidate, in adult participants aged 60 years and older. In addition, the study will evaluate the safety and immunogenicity of a booster vaccination administered 12 months after the primary vaccination in a subset of the study population.

Detailed Description
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Study duration per participant: 12 months for the Sentinel and Main Cohorts and 24 months overall for the subset of participants enrolled in the Booster Cohort. Treatment Duration: Sentinel Cohort: 1 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 (Main Cohort). Participants will be followed for 12 months after administration of the booster dose.

Official Title
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A Phase I/IIa, Randomized, Observer-blind Placebo-controlled Multi-arm Study to Evaluate the Safety and Immunogenicity of an RSV/hMPV Vaccine, in Adult Participants Aged 60 Years and Older

Conditions
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Respiratory Syncytial Virus Infection, Healthy Volunteers, Human Metapneumovirus

Intervention / Treatment
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* Biological: RSV/hMPV vaccine candidate Dose L
* Biological: RSV/hMPV vaccine candidate Dose A
* Biological: RSV/hMPV vaccine candidate Dose B
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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. Participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion Note: Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Any screening laboratory parameter with laboratory abnormalities deemed clinically significant by the investigator Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy. 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 mRNA coronavirus disease 2019 (COVID-19) vaccine History of RSV and/or hMPV-associated illness, diagnosed clinically, 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 Thrombocytopenia or bleeding disorder, contraindicating intramuscular (IM) injection based on investigator's judgment Receipt of anticoagulants in the 3 weeks preceding inclusion 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 History of acute infection symptoms or a positive severe acute respiratory syndrome coronavirus reverse transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) or antigen test in the 10 days prior to the visit. A prospective participant should not be included in the study until the condition has resolved 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 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 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 The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose-escalation (Phase I, sentinel cohort), parallel (Phase IIa, main cohort), multi-center
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sentinel Cohort: RSV/hMPV Group 0 (Dose L)<br>Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate | Biological: RSV/hMPV vaccine candidate Dose L<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Experimental: Sentinel Cohort: RSV/hMPV Group 1 (Dose A)<br>Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate | Biological: RSV/hMPV vaccine candidate Dose A<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Experimental: Sentinel Cohort: RSV/hMPV Group 2 (Dose B)<br>Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate | Biological: RSV/hMPV vaccine candidate Dose B<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Placebo Comparator: Sentinel Cohort: Placebo-Group 3<br>Participants will be randomized to receive a single IM injection of placebo | Biological: Placebo<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Experimental: Main Cohort: RSV/hMPV Group 1 (Dose A)<br>Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate | Biological: RSV/hMPV vaccine candidate Dose A<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Experimental: Main Cohort: RSV/hMPV Group 2 (Dose B)<br>Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate | Biological: RSV/hMPV vaccine candidate Dose B<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Placebo Comparator: Main Cohort: Placebo-Group 3<br>Participants will be randomized to receive a single IM injection of placebo | Biological: Placebo<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Experimental: Booster Cohort-RSV/hMPV<br>Participants will be randomized to receive a determined dose of single IM injection of RSV/hMPV vaccine candidate from a subset of Main cohort | Biological: RSV/hMPV vaccine candidate Dose A<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>Biological: RSV/hMPV vaccine candidate Dose B<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|
| Placebo Comparator: Booster Cohort-Placebo<br>Participants will be randomized to receive of single IM injection of placebo from a subset of Main cohort | Biological: Placebo<br>* Pharmaceutical form:Suspension for injection-Route of administration:Intramuscular Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of unsolicited systemic immediate adverse events (AEs) | Number of participants experiencing immediate an immediate unsolicited systemic adverse event | Within 30 minutes after primary vaccination | 
| Presence of solicited injection site or systemic reactions | Number of participants reporting: injection site reactions: pain, erythema and swelling systemic reactions: fever, headache, fatigue, myalgia, arthralgia and chills | Within 7 days after primary vaccination | 
| Presence of unsolicited AEs | Number of participants experiencing unsolicited AEs | Within 28 days after vaccination | 
| Presence of medically attended adverse events (MAAEs) | Number of participants experiencing MAAEs | Up to 6 months after primary injection | 
| Presence of serious adverse events (SAEs) | Number of participants experiencing SAEs | Up to 6 months after primary injection | 
| Presence of adverse events of special interest (AESIs) | Number of participants experiencing AESIs | Up to 6 months after primary injection | 
| Presence of related SAEs | Number of participants experiencing related SAEs | Throughout study (approximately 24 months) | 
| Presence of related AESIs | Number of participants experiencing related AESIs | Throughout study (approximately 24 months) | 
| Presence of fatal SAEs | Number of participants experiencing fatal SAEs | Throughout study (approximately 24 months) | 
| Presence of out-of-range biological test results | Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test, including shift from baseline values) | Within 7 days after vaccination | 
| RSV-A serum neutralizing antibody (nAb) titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) in Phase IIa (Main/Booster Cohort) | RSV-A serum neutralizing antibody (nAb) titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) | Day 1 and Day 29 | 
| hMPV serum nAb titers at pre-vaccination (D01), 28 days post-primary vaccination (D29) in Phase IIa (Main/Booster Cohort) | hMPV serum nAb titers at pre-vaccination (D01), 28 days post-primary vaccination (D29) | Day 1 and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV-A serum neutralizing antibody (nAb) titers at pre-vaccination (D01) and 28 days post-primary vaccination (D29) | RSV-A serum nAb titers at pre-vaccination (D01), 28 days (D29) post-primary vaccination | Day 1 and Day 29 | 
| RSV-B serum neutralizing antibody (nAb) titers at pre-vaccination (D01) and 28 days post-primary vaccination (D29) | RSV-B serum nAb titers at pre-vaccination (D01), 28 days (D29) post-primary vaccination | Day 1 and Day 29 | 
| hMPV serum nAb titers at pre vaccination (D01), 28 days post-primary vaccination (D29) | hMPV serum nAb titers at pre-vaccination (D01), 28 days (D29) post-primary vaccination | Day 1 and Day 29 | 
| RSV A serum nAb titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | RSV A serum nAb titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| RSV B serum nAb titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | RSV B serum nAb titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| RSV A serum anti-F immunoglobulin G (IgG) antibody (Ab) titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | RSV A serum anti-F immunoglobulin G (IgG) antibody (Ab) titers at pre-vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| hMPV A serum nAb titers at pre vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | hMPV A serum nAb titers at pre vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| hMPV A serum anti-F IgG Ab titers at pre vaccination (D01), 28 days (D29), 3, 6, 9 and 12 months post-primary vaccination | hMPV A serum anti-F IgG Ab titers at pre vaccination (D01), 28 days (D29), 3 months (D91), and 6 months (D181) post vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| RSV A serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-booster vaccination | RSV A serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-booster vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| RSV B serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-booster vaccination | RSV B serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-booster vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| RSV A serum anti-F IgG Ab titers at pre-booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post- booster vaccination | RSV A serum anti-F IgG Ab titers at pre-booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post- booster vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| hMPV A serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post booster vaccination | hMPV A serum nAb titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post-booster vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 | 
| hMPV serum anti-F IgG Ab titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post booster vaccination | hMPV serum anti-F IgG Ab titers at pre booster vaccination (D01), 28 days (D29), and 3, 6, 9, and 12 months post- booster vaccination | Day 1, Day 29, Month 3, Month 6, Month 9 and Month 12 |