Safety and Immunogenicity of CodaVax-RSV in Seropositive and Seronegative Children

Study Overview
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Brief Summary
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This study is a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation clinical trial to evaluate the safety of and immune response to CodaVax-RSV in healthy children. They will be vaccinated in spring to early autumn 2023 and followed through the 2023-24 RSV season. 18 children aged 2 to 5 years who are RSV-seropositive (have antibodies to RSV) and 33 children aged 6 months to < 2 years who are RSV-seronegative (do not have antibodies to RSV) will be enrolled in escalating-dose cohorts. A safety committee will review the safety profile of each dosing group before the next dose-escalation. Children will receive 2 doses of the vaccine at one of several dose levels or placebo (saline solution with no active ingredient) as nose drops; doses will be 28 days apart. A parent/guardian will record temperature and other conditions in a diary daily for 7 days after each dose. The parent/guardian will be contacted by telephone on the day after Dose 1 for safety assessment and review of the diary data. Children will return to the clinic 3, 7, 14, and 28 days after each dose. The parent/guardian will then be contacted by telephone monthly until 1 year after the second dose. Study procedures include physical examinations, vital signs, and collections of blood and nose/throat swab samples to look at safety of the vaccine and to analyze body's immune response.

Official Title
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Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating Safety and Immunogenicity of CodaVax-RSV in Seropositive and Seronegative Children

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: CodaVax-RSV
* Biological: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at the time of informed consent: Part A: 2 to 5 years, inclusive Part B: 6 months to < 2 years RSV Status at Screening: Part A: RSV-seropositive Part B: RSV-seronegative Good general health status Product of normal full-term pregnancy (36 to 42 weeks gestation) Exclusion Criteria: Household contact with any of the following groups of individuals for the period up to 14 days after each dose: Pregnant women Infants < 6 months of age With hospitalization for asthma or other chronic respiratory disease in the past 5 years Immunocompromised individuals, which includes, but is not limited to, those with the following conditions: AIDS Receipt of chemotherapy within the past 6 months Current receipt of immunosuppressive agents Solid organ or bone marrow transplant Enrolled in the same classroom at full-time day care with infants < 6 months of age for 14 days after each dose Household contact of another child enrolled into the study Inadequate venous access for repeated phlebotomy Height and weight ≤ 5th percentile for age and sex (according to CDC growth charts for children in Part A, according to World Health Organization Child Growth Standards for children in Part B)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo comparator<br>Administered as nose drops | Biological: Normal Saline<br>* Placebo comparator<br>|
| Experimental: Experimental: CodaVax-RSV 10^6 PFU<br>Respiratory syncytial virus live attenuated vaccine against RSV administered as nose drops | Biological: CodaVax-RSV<br>* live attenuated vaccine against RSV<br>|
| Experimental: Experimental: CodaVax-RSV 10^5 PFU<br>Respiratory syncytial virus live attenuated vaccine against RSV administered as nose drops | Biological: CodaVax-RSV<br>* live attenuated vaccine against RSV<br>|
| Experimental: Experimental: CodaVax-RSV 10^4 PFU<br>Respiratory syncytial virus live attenuated vaccine against RSV administered as nose drops | Biological: CodaVax-RSV<br>* live attenuated vaccine against RSV<br>|
| Experimental: Experimental: CodaVax-RSV 10^3 PFU<br>Respiratory syncytial virus live attenuated vaccine against RSV administered as nose drops | Biological: CodaVax-RSV<br>* live attenuated vaccine against RSV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting expected adverse reactions | Reactogenicity Event Counts | Day 7 | 
| Number of participants reporting expected adverse reactions | Reactogenicity Event Counts | Day 36 | 
| Number of participant reported adverse events | Adverse event counts | Days 57 | 
| Number of participants with Medically attended AEs (MAAEs), new-onset chronic illnesses (NCIs), and serious AEs (SAEs) | counts | Days 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody | Neutralizing antibody level | Screening, Days 29 and 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, Live-attenuated vaccine, respiratory infection, Pediatric, Codon-deoptimized