A Study to Learn About the Safety and Immune Activity of RSVpreF in Children Who Are at High Risk of Getting RSV Disease

Study Overview
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Brief Summary
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The purpose of this study is to learn about the safety and immune activity of the vaccine (called RSVpreF) in children 2 to <18 years of age who are at high risk of RSV disease. Phase 1 will identify the dose level to be used in Phase 2/3. In this phase, all participants will receive one injection of RSVpreF. Phase 1 has four study visits, two in-clinic and two telehealth visits. Blood samples will be collected for testing. This phase is about 6 months long for each participant and will be conducted in the United States. Phase 2/3 will evaluate the selected dose level from Phase 1 in a large number of children to collect more information about the safety of the vaccine and the amount of antibodies produced by the vaccine. In this Phase, all participants will receive either RSVpreF or placebo and will not know which they have received until the end of study. Phase 2/3 will have three scheduled in-clinic visits. Blood samples will be collected for testing. This phase is about 6 months long for each participant.

Official Title
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A PHASE 1, OPEN-LABEL, AGE-DESCENDING, DOSE-FINDING STUDY AND A PHASE 2/3, PLACEBO-CONTROLLED, RANDOMIZED, DOUBLE-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF RESPIRATORY SYNCYTIAL VIRUS PREFUSION F SUBUNIT VACCINE (RSVpreF) IN CHILDREN 2 TO <18 YEARS OF AGE AT HIGH RISK OF RSV DISEASE

Conditions
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RESPIRATORY SYNCYTIAL VIRUS (RSV)

Intervention / Treatment
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* Biological: RSVpreF 120 µg
* Biological: RSVpreF 60 µg
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants 2 to <18 years of age at enrollment Phase 1 only: Participants 2 to <18 years of age should either be healthy or be considered by the investigator to be at high risk of RSV disease based on the presence of 1 of the following chronic medical conditions: Cystic fibrosis Medically treated asthma Other chronic respiratory diseases and malformations of the lung Down syndrome Neuromuscular disease Cerebral palsy Hemodynamically significant or symptomatic congenital heart disease Phase 2 and 3 only: Participants 5 to <18 years of age should be considered by the investigator to be at high risk of RSV disease based on the presence of 1 of the chronic medical conditions listed below. Participants 2 to <5 years of age may be enrolled with, but are not required to have, 1 of the following chronic medical conditions: Cystic fibrosis Medically treated asthma Other chronic respiratory diseases and malformations of the lung Down syndrome Neuromuscular disease Cerebral palsy Hemodynamically significant or symptomatic congenital heart disease Phase 1 only: All participants 2 to <5 years of age must be seropositive for RSV as confirmed by serology. Participants' parent(s)/legal guardian(s) and participants, as age appropriate, who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, and other study procedures, including collection of nasal swabs by participants' parent(s)/legal guardian(s) and by study staff when indicated. The participant's parent(s)/legal guardian is capable of giving signed informed consent as described in the protocol. Depending on the age of the participant and according to local requirements, participants will also be asked to provide assent as appropriate (verbal or written). Exclusion Criteria: Immunocompromised individuals associated with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus. Note: Stable type 1 diabetes and hypothyroidism are permitted. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Individuals with a history of epilepsy or other seizure disorders, or a history of seizures and/or other neurological complications following vaccination. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation. Children who may have been exposed to investigational RSV vaccines through maternal immunization will be permitted. Receipt of investigational or approved monoclonal antibodies against RSV within 6 months before study intervention administration, or planned receipt throughout the study. Receipt of blood/plasma products or immunoglobulins within 28 days before study intervention administration, or planned receipt throughout the study. Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before study intervention administration, or planned receipt throughout the study. Note: Systemic corticosteroids are defined as those administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune disease). Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) corticosteroids are permitted. Participation in other studies involving study intervention within 28 days prior to study entry and/or for the duration of study participation. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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: Phase 1 is an open-label dose-finding study. A single dose of RSVpreF 120 µg will be given to 40 participants in the 5 to <18 age group first. Upon safety review and approval, a dose of 60 µg will be given to 20 participants in the 2 to <5 age group. If, 60 µg is safe, another 20 participants in the 2 to <5- age group will receive the 120-µg dose. Approximately 60 to 120 participants are expected to be enrolled in the Phase 1. Phase 2/3 will evaluate the safety and immunogenicity of each selected dose level from Phase 1. Within each age group, participants will be randomized in a 2:1 ratio to receive active vaccine or placebo. If the same dose level is selected for both age groups, a total of 930 participants will be enrolled, with at least 75 with chronic medical conditions in the older age group. If different dose levels are selected for the 2 age groups, 930 participants in each age group will be enrolled.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard dose in 5 to <18 years olds, healthy<br>standard dose (120 µg) | Biological: RSVpreF 120 µg<br>* RSVpreF standard dose level<br>|
| Experimental: standard dose in 5 to < 18 years olds, with chronic high risk conditions<br>standard dose (120 µg) | Biological: RSVpreF 120 µg<br>* RSVpreF standard dose level<br>|
| Experimental: standard dose in 2 to < 5 years olds<br>standard dose (120 µg) | Biological: RSVpreF 120 µg<br>* RSVpreF standard dose level<br>|
| Experimental: low dose in 5 to <18 years olds, healthy<br>low dose (60 µg) | Biological: RSVpreF 60 µg<br>* RSVpreF low dose level<br>|
| Experimental: low dose in 5 to <18 years olds, with chronic high risk conditions<br>low dose (60 µg) | Biological: RSVpreF 60 µg<br>* RSVpreF low dose level<br>|
| Experimental: low dose in 2 to < 5 years olds<br>low dose (60 µg) | Biological: RSVpreF 60 µg<br>* RSVpreF low dose level<br>|
| Experimental: RSVpreF standard dose<br>with dose selected from phase 1 to be used in phase 2/3 | Biological: RSVpreF 120 µg<br>* RSVpreF standard dose level<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: placebo<br>* Placebo<br>|
| Experimental: RSVpreF low dose<br>with dose selected from phase 1 to be used in phase 2/3 | Biological: RSVpreF 60 µg<br>* RSVpreF low dose level<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Primary Safety - The proportion of participants reporting local reactions | Local reactions include pain at injection site, redness and swelling reported on e-diaries. | Within 7 days following study administration intervention | 
| Phase 1: Primary Safety - The proportion of participants reporting systemic reactions | Systemic reactions: fever, fatigue/tiredness, headache, muscle pain, joint pain, vomiting, diarrhea reported on e-diaries. | Within 7 days following study administration intervention | 
| Phase 1: Primary Safety - The proportion of participants reporting Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs include both serious and non-serious adverse events. | Through 1 month following study administration intervention | 
| Phase 1: Primary Safety - The proportion of participants reporting Serious Adverse Events (SAEs) | SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Throughout the study duration (approximately 6 months) | 
| Phase 1: Primary Safety - The proportion of participants reporting Newly Diagnosed Chronic Medical Conditions (NDCMCs) | An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects. | Throughout the study duration (approximately 6 months) | 
| Phase 2/3: Primary Safety - The proportion of participants reporting local reactions | Local reactions include pain at injection site, redness and swelling reported on e-diaries. | Within 7 days following study administration intervention | 
| Phase 2/3: Primary Safety - The proportion of participants reporting systemic reactions | Systemic reactions: fever, fatigue/tiredness, headache, muscle pain, joint pain, vomiting, diarrhea reported on e-diaries. | Within 7 days following study administration intervention | 
| Phase 2/3: Primary Safety - The proportion of participants reporting Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs include both serious and non-serious adverse events. | Through 1 month following study administration intervention | 
| Phase 2/3: Primary Safety - The proportion of participants reporting Serious Adverse Events (SAEs) | SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Throughout the study duration (approximately 6 months) | 
| Phase 2/3: Primary Safety - The proportion of participants reporting Newly Diagnosed Chronic Medical Conditions (NDCMCs) | An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects. | Throughout the study duration (approximately 6 months) | 
| Phase 2/3: Primary Immunogenicity - GMT ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B serum (Neutralizing Titers) NTs with RSVpreF in Study C3671016 participants to that in Study C3671013 adults ≥60 years of age. | RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs). GMT ratio (GMR) of the GMTs for RSV A and RSV B serum NTs with RSVpreF in Study C3671016 participants to that in Study C3671013 adults ≥60 years of age. | 1 month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Secondary Immunogenicity - GMT of NTs for RSV A and RSV B | RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs). | At each blood sampling visit (Day 1 before vaccination and 1-month after vaccination) | 
| Phase 1: Secondary Immunogenicity - GMFR of NTs for RSV A and RSV B | RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Fold Rise (GMFR). | At each blood sampling visit (Day 1 before vaccination and 1-month after vaccination) | 
| Phase 1: Secondary Immunogenicity - Median frequencies of RSV F antigen-specific CD4+ T cells expressing IFN gamma | As measured at the central laboratory, RSV F antigen-specific CD4+ T cells secreting IFN gamma | At each blood sampling visit (Day 1 before vaccination and 1-month after vaccination) | 
| Phase 1: Secondary Immunogenicity - Median frequencies of RSV F antigen-specific CD4+ T cells expressing IL-4 | As measured at the central laboratory, RSV F antigen-specific CD4+ T cells secreting IL-4 | At each blood sampling visit (Day 1 before vaccination and 1-month after vaccination) | 
| Phase 2/3: Secondary Immunogenicity - GMT of NTs for RSV A and RSV B | RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs). | At each blood sampling visit (Day 1 before vaccination, 1-month and 6 month after vaccination) | 
| Phase 2/3: Secondary Immunogenicity - GMFR of NTs for RSV A and RSV B | RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Fold Rise (GMFR). | At each blood sampling visit (Day 1 before vaccination, 1-month and 6 month after vaccination) | 
| Phase 2/3: Secondary Immunogenicity - GMCs of IgG for RSV A and RSV B | RSV A and RSV B prefusion F-binding IgG, expressed as Geometric Mean Concentrations (GMCs). | At each blood sampling visit (Day 1 before vaccination, 1-month and 6 month after vaccination) | 
| Phase 2/3: Secondary Immunogenicity - GMFR of IgG for RSV A and RSV B | RSV A and RSV B prefusion F-binding IgG, expressed as Geometric Mean Fold Rise (GMFR). | At each blood sampling visit (Day 1 before vaccination, 1-month and 6 month after vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RESPIRATORY SYNCYTIAL VIRUS, RSV, RSV vaccine, Respiratory illness, Respiratory infection, Pediatric