Study of a Respiratory Syncytial Virus mRNA Candidate With 2 Different Lipid Nanoparticle-based Formulations in Adults Aged 18 to 50 Years and 60 Years and Older

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 3 dose-levels of a respiratory syncytial virus (RSV) messenger ribonucleic acid (mRNA) vaccine candidate formulated with 2 different lipid nanoparticles (LNPs) (ie, LNP containing CL-0059 or CL-0137) in healthy adult participants aged between 18 and 50 years, and 60 years and older. The primary objectives of this study are to assess the safety and immunogenicity profiles across the dose-level groups (low, medium, and high doses) with 2 LNPs (CL-0059 and CL-0137). 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. The duration of each participant's participation is 12 months for the Sentinel and Main Cohorts and 24 months overall for the subset of participants enrolled in the Booster Cohort.

Detailed Description
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The duration of each participant's participation is 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 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.

Official Title
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A Phase I/II, Randomized, Placebo-controlled Multi-arm Dose-finding Study to Evaluate the Safety and Immunogenicity of a RSV mRNA Vaccine Candidate With Either LNP CL-0059 or LNP CL-0137 in Adult Participants 18 to 50 Years of Age in a Sentinel Cohort and 60 Years and Older in Main and Booster Cohorts

Conditions
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Respiratory Syncytial Virus Immunization

Intervention / Treatment
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* Biological: RSV mRNA LNP CL-0059 Low dose
* Biological: RSV mRNA LNP CL-0137 Low dose
* Biological: RSV mRNA LNP CL-0059 Medium Dose
* Biological: RSV mRNA LNP CL-0137 Medium Dose
* Biological: RSV mRNA LNP CL-0059 High Dose
* Biological: RSV mRNA LNP CL-0137 High RSV mRNA LNP CL-0137 High Dose Dose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sentinel Cohort: Aged 18 to 50 years on the day of inclusion Main Cohort: Aged 60 years or older on the day of inclusion 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.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Sequential (Phase I)/ parallel (Phase II)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0059 vaccine (Low dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0059 Low dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Experimental: Group 2: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0137 vaccine (Low dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0137 Low dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Experimental: Group 3: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0059 vaccine (Medium dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0059 Medium Dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Experimental: Group 4: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0137 vaccine (Medium dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0137 Medium Dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Experimental: Group 5: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0059 vaccine (High dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0059 High Dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Experimental: Group 6: Sentinel and Main Cohorts<br>1 injection of RSV mRNA LNP CL-0137 vaccine (High dose) via intramuscular injection | Biological: RSV mRNA LNP CL-0137 High RSV mRNA LNP CL-0137 High Dose Dose<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection<br>|
| Placebo Comparator: Group 7: Main, Sentinel and Booster Cohorts<br>1 injection of placebo via intramuscular injection | Other: Placebo<br>* Pharmaceutical Form: Liquid 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 immediate adverse events (AEs) | Number of participants experiencing immediate an immediate adverse event | Within 30 minutes after vaccination | 
| Presence of solicited injection site or systemic reactions | Number of participants reporting: injection site reactions: pain, erythema and swelling systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills | Within 7 days after 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 | Within 28 days after vaccination | 
| Presence of serious adverse events (SAEs) | Number of participants experiencing SAEs | Month 12 | 
| Presence of adverse events of special interest (AESIs) | Number of participants experiencing AESIs | Month 12 | 
| 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) | Within 7 days after vaccination | 
| Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 1 | Nab titers post-primary vaccination | Day 1 | 
| Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29 | Nab titers post-primary vaccination | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of immediate adverse events post-booster vaccination | Number of participants experiencing immediate an immediate adverse event | Within 30 minutes after vaccination | 
| Presence of solicited injection site or systemic reactions post-booster vaccination | Number of participants reporting: injection site reactions: pain, erythema and swelling systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills | Within 7 days after vaccination | 
| Presence of unsolicited AEs post-booster vaccination | Number of participants experiencing unsolicited AEs | Within 28 days after vaccination | 
| Presence of medically attended adverse events post-booster vaccination | Number of participants experiencing MAAEs | Within 28 days after vaccination | 
| Presence of serious adverse events (SAEs) post-booster vaccination | Number of participants experiencing SAEs | Throughout the booster study, approximately 12 months | 
| Presence of adverse events of special interest post-booster vaccination | Number of participants experiencing AESIs | Throughout the booster study, approximately 12 months | 
| Presence of out-of-range biological test results post-booster vaccination | Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test) | Within 7 days after vaccination | 
| RSV-A serum 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), and 3, 6, and 12 months post-primary vaccination | 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 | Serum anti-F IgG Ab titers at pre-vaccination (D01), 28 days (D29), and 3, 6, and 12 months post-primary vaccination | Day 1, Day 29, Month 3, Month 6 and Month 12 | 
| GMTs of RSV-A serum nAb post-booster vaccination | RSV-A serum nAb titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post-booster vaccination | Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster | 
| GMTs of serum anti-F IgG Ab titers post-booster vaccination | Serum anti-F IgG Ab titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post- booster vaccination | Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster |