Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seronegative Children 6-36 Months

Study Overview
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Brief Summary
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This study evaluates an investigational vaccine that is designed to protect humans against infection with respiratory syncytial virus (RSV) and is administered as a nasal spray. Specifically, the study analyzes the safety of, and the immune response to, the vaccine when administered to healthy children between the ages of 6 and 24 months who are seronegative to RSV.

Official Title
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Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Phase 1c Study to Evaluate the Safety and Immunogenicity of an Intranasal Live Attenuated Respiratory Syncytial Virus Vaccine (MV-012-968) in Seronegative Children 6-36 Months

Conditions
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Respiratory Syncytial Virus (RSV)

Intervention / Treatment
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* Biological: Investigational RSV vaccine MV-012-968 (Dosage 1)
* Biological: Investigational RSV vaccine MV-012-968 (Dosage 2)
* Biological: Investigational RSV vaccine MV-012-968 (Dosage 3; single-dose)
* Biological: Investigational RSV vaccine MV-012-968 (Dosage 3; two-dose)
* Other: Placebo (single-dose)
* Other: Placebo (two-dose)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Children aged 6-36 months Good health based on history, physical examination, and medical record review, without evidence or suspicion of chronic disease Seronegative to RSV, as defined by serum nAb titer below the threshold described in the study protocol and operations manual Written informed consent provided by parent(s)/guardian(s) Key Exclusion Criteria: Known or suspected chronic illness, particularly cardiopulmonary (including asthma or reactive airways disease), genetic or metabolic, hepatic, renal, infectious (including recurrent or chronic sinusitis), or immunodeficiency Prior lab-confirmed RSV infection Household or close contact (including but not limited to daycare) during the 21 days post-inoculation with anyone < 6 months old or immunocompromised (applies to first study inoculation) Nasal obstruction (including due to anatomic/structural causes, acute or chronic rhinosinusitis, or other causes) Receipt of immunoglobulins, monoclonal antibodies and/or any blood products, or ribavirin within 6 months prior to study inoculation, or planned use during study period Receipt of an investigational RSV vaccine at any time Any other condition that, in the judgment of the investigator, would be a risk to subject's safety and/or may interfere with study procedures or interpretation of results

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

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: 1st 5 subjects will be in Group 1 and randomized to investigational vaccine (IP) Dosage 1 or placebo. Safety Monitoring Committee (SMC) will review Group 1 data to Day 15 to allow dose escalation. Next 10 subjects will be in Group 2 and randomized to IP Dosage 2 or placebo. SMC will review Group 2 data to Day 15 to allow dose escalation. Next 12 enrolled subjects will be in Group 3 and randomized to IP Dosage 3 or placebo. SMC will review Group 3 data to Day 15 to allow dose escalation. Next 12 subjects will be in Group 4 and randomized to IP Dosage 4 or placebo. SMC will review Group 4 data to Day 15 to allow dose escalation. Next 12 subjects will be in Group 3a and randomized to IP Dosage 3 or placebo; if meet criteria will receive 2nd dose IP or placebo 28 days after 1st dose. Final 12 subjects will be in Group 4a and randomized to IP Dosage 4 or placebo; if meet criteria will receive 2nd dose IP or placebo 28 days after 1st dose.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dosage Group 1: RSV Vaccine Dosage 1<br>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 1 | Biological: Investigational RSV vaccine MV-012-968 (Dosage 1)<br>* Single dose administered intranasally on Day 1<br>|
| Experimental: Dosage Group 2: RSV Vaccine Dosage 2<br>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 2 | Biological: Investigational RSV vaccine MV-012-968 (Dosage 2)<br>* Single dose administered intranasally on Day 1<br>|
| Experimental: Dosage Group 3: RSV Vaccine Dosage 3 (Single-dose)<br>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 3 | Biological: Investigational RSV vaccine MV-012-968 (Dosage 3; single-dose)<br>* Single dose administered intranasally on Day 1<br>|
| Experimental: Dosage Group 3a: RSV Vaccine Dosage 3 (Two-dose)<br>Participants in this arm will receive a single intranasal dose of the investigational RSV vaccine at Dosage 3 followed by a second identical dose of the investigational RSV vaccine 28 days later | Biological: Investigational RSV vaccine MV-012-968 (Dosage 3; two-dose)<br>* Single dose administered intranasally on Day 1, followed by an identical dose administered intranasally at the Day 29 study visit<br>|
| Placebo Comparator: Placebo (Single-dose)<br>Participants in this arm will receive a single intranasal dose of placebo | Other: Placebo (single-dose)<br>* Single dose administered intranasally on Day 1<br>|
| Placebo Comparator: Placebo (Two-dose)<br>Participants in this arm will receive a single intranasal dose of placebo followed by a second identical dose of placebo 28 days later | Other: Placebo (two-dose)<br>* Single dose administered intranasally on Day 1, followed by an identical dose administered intranasally at the Day 29 study visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse events (AEs) | Frequency of solicited AEs will be measured, categorized by severity. Solicited AEs are predefined AEs that may occur after investigational vaccine administration | Immediate post-vaccination period | 
| Unsolicited AEs | Frequency of unsolicited AEs will be measured, categorized by severity. Unsolicited AEs are any untoward medical occurrences in a participant administered the investigational vaccine, regardless of causal relationship to the investigational vaccine. Unsolicited AEs can include unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of the investigational vaccine. | Immediate post-vaccination period | 
| Serious adverse events (SAEs) | Frequency of SAEs will be measured, categorized by vaccine-relatedness . SAEs are AEs, whether considered causally related to the investigational vaccine or not, that threaten life or result in any of the following: death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect. | Full study duration, an average of 1 year | 
| Medically attended adverse events (MAEs) | Frequency of MAEs will be measured, categorized by vaccine-relatedness. MAEs are AEs, whether considered causally related to the investigational vaccine or not, with unscheduled medically attended visits, such as urgent care visits, acute primary care visits, emergency department visits, or other previously unplanned visits to a medical provider. Scheduled medical visits such as routine physicals, wellness checks, 'check-ups', and vaccinations, are not considered MAEs. | Full study duration, an average of 1 year | 
| Change in RSV-specific serum neutralizing antibody (nAb) titers (GMT) | Change in serum RSV-specific neutralizing antibody (nAb) titers will be measured per participant. | Baseline through Day 28, an average of six (6) weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum binding (RSV F-specific) Immunoglobulin G (IgG) concentrations | Change in serum binding (RSV F-specific) IgG concentrations will be measured per participant | Baseline through Day 28, an average of six (6) weeks | 
| Change in nasal mucosal binding (RSV F-specific) Immunoglobulin A (IgA) concentrations | Change in nasal mucosal binding (RSV F-specific) IgA concentrations will be measured per participant | Baseline through Day 28, an average of six (6) weeks | 
| Potential vaccine virus shedding after a single intranasal dose of MV-012-968: frequency | Frequency of any post-vaccination shedding of vaccine virus (as detected by plaque assay) after a single intranasal dose of MV-012-968 will be measured per dosage group and overall. | Intranasal inoculation through Day 22, an average of three (3) weeks | 
| Potential vaccine virus shedding after a single intranasal dose of MV-012-968: magnitude | If post-vaccination shedding of vaccine virus is detected by plaque assay after a single intranasal dose of MV-012-968, peak viral titer (measured in plaque forming units, PFU) will be measured per dosage group and overall | Intranasal inoculation through Day 22, an average of three (3) weeks | 
| Potential vaccine virus shedding after a single intranasal dose of MV-012-968: duration | If post-vaccination shedding of vaccine virus is detected by plaque assay after a single intranasal dose of MV-012-968, duration of shedding (in days) will be measured per dosage group and overall. | Intranasal inoculation through Day 22, an average of three (3) weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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live attenuated vaccine, safety, immunogenicity, Phase 1 clinical trial, Pediatric, seronegative, children