Study of the Safety and Immunogenicity of an Intranasal Vaccine for Respiratory Syncytial Virus in Seropositive Children

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 drops in the nose. Specifically, the study analyzes the safety of, and the immune response to, the vaccine when administered to healthy children between the ages of 15 and 59 months who are seropositive to RSV.

Official Title
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A Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Phase 1b Study to Evaluate the Safety and Immunogenicity of an Intranasal Live Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Seropositive Young Children

Conditions
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Respiratory Syncytial Virus Infections

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Children aged 15-59 months Good health based on history, physical examination and medical record review, without evidence or suspicion of chronic disease Seropositive to RSV, as defined by serum neutralizing antibody titer above the threshold described in the study Analytical Plan 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), metabolic, hepatic, renal, or infectious (including recurrent or chronic sinusitis) Known or suspected immunodeficiency Household or close contact with anyone ≤ 6 months of age or with immunocompromised individual(s) 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 3 months prior to study inoculation, or planned 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 participant's safety and/or may interfere with study procedures or interpretation of results

Ages Eligible for Study
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Minimum Age: 15 Months
Maximum Age: 59 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: The first 15 enrolled participants will be assigned to Dosage Group 1 and be randomly allocated to receive either investigational vaccine at Dosage 1 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 1 safety data through Day 14, to allow dosage escalation. The next 15 enrolled participants will be assigned to Dosage Group 2 and be randomly allocated to receive investigational vaccine at Dosage 2 or placebo. The Safety Monitoring Committee will subsequently review Dosage Group 2 safety data through Day 14, to allow dosage escalation. The final group (Dosage Group 3) will consist of up to 12 enrolled participants who will be allocated to receive investigational vaccine at Dosage 3.
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>|
| Placebo Comparator: Dosage Group 1: Placebo<br>Participants in this arm will receive a single intranasal dose of placebo. | Other: Placebo<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>|
| Placebo Comparator: Dosage Group 2: Placebo<br>Participants in this arm will receive a single intranasal dose of placebo. | Other: Placebo<br>* Single dose administered intranasally on Day 1<br>|
| Experimental: Dosage Group 3: RSV Vaccine Dosage 3<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)<br>* Single dose administered intranasally on Day 1<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 6 months | 
| 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 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum RSV-specific neutralizing antibody titers | Change in serum RSV-specific neutralizing antibody (nAb) titers will be measured per participant. | Baseline through Day 28, an average of six (6) weeks | 
| Change in serum binding (RSV F-specific) antibody titers | Change in serum binding (RSV F-specific) antibody titers will be measured per participant. | Baseline through Day 28, an average of six (6) weeks | 
| Change in nasal mucosal binding (RSV F-specific) antibody titers | Change in mucosal binding (RSV F-specific) antibody titers will be measured per participant. | Baseline through Day 28, an average of six (6) weeks | 
| Potential vaccine virus shedding: frequency | Frequency of any post-vaccination shedding of vaccine virus (as detected by viral culture) will be measured per dosage group and overall. | Baseline through Day 28, an average of four (4) weeks | 
| Potential vaccine virus shedding: magnitude | If post-vaccination shedding of vaccine virus is detected by culture, peak viral titer (measured in plaque forming units, PFU) will be measured per dosage group and overall. | Baseline through Day 28, an average of four (4) weeks | 
| Potential vaccine virus shedding: duration | If post-vaccination shedding of vaccine virus is detected by culture, duration of shedding (in days) will be measured per dosage group and overall. | Baseline through Day 28, an average of four (4) weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Phase 1 clinical trial, Pediatric, Seropositive, Live attenuated vaccine, Safety