PROtocol for Coxsackievirus VaccinE in Healthy VoluNTteers

Study Overview
=================
Brief Summary
-----------------
Phase 1, first-in-human, randomized, double-blind, placebo-controlled, multiple-dose-escalation study to evaluate the safety, tolerability and immunogenicity of PRV-101, a coxsackie virus B vaccine, in healthy volunteers.

Detailed Description
-----------------
Thirty two healthy adult subjects will be enrolled into 2 dose cohorts (low-dose and high-dose cohorts, 16 subjects per cohort) and will be randomized in a double-blind manner to PRV-101 or placebo in a 3:1 ratio. Each subject will receive up to 3 administrations of the study drug (PRV-101 or placebo) at 4-week intervals and will be followed for 24 weeks after the final dose. Each cohort will start with a sentinel dosing group (2 subjects). Cohort 2 will commence after safety data from the first 2 doses from all Cohort 1 participants are reviewed.

Official Title
-----------------
A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of PRV-101, a Coxsackie Virus B (CVB) Vaccine, in Healthy Adult Subjects

Conditions
-----------------
Viral; Infection, Coxsackie(Virus)

Intervention / Treatment
-----------------
* Biological: PRV-101
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults, males and females, ages 18 to 45 yrs, with BMI 19 to 30 kg/m2 Women of childbearing potential must have negative pregnancy test and agree to use an acceptable method of highly effective contraceptive Men must either have a vasectomy or agree to use highly effective contraception Exclusion Criteria: Prior or current clinically significant medical illness or disorder Has celiac disease or type 1 diabetes or related autoantibodies Has active acute or chronic/latent infection, or history of recent serious infection Recent acute illness or recent major illness, hospitalization or surgery Recent history of alcohol or drug abuse Received an experimental antibody or biologic therapy in last 6 months Received live, inactivated or subunit virus vaccine or a bacterial vaccine within last 4 weeks Intolerance or hypersensitivity to vaccines or vaccine components or has a drug or food allergy or allergic disease requiring medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1, Low Dose, Placebo<br>Low dose of placebo by intramuscular injection, 3 doses at 4-week intervals | Other: Placebo<br>* Placebo<br>|
| Experimental: Cohort 1, Low Dose, PRV-101<br>Low dose of PRV-101 by intramuscular injection, 3 doses at 4-week intervals | Biological: PRV-101<br>* Coxsackie Virus B vaccine<br>|
| Placebo Comparator: Cohort 2, High Dose, Placebo<br>High dose of placebo by intramuscular injection, 3 doses at 4-week intervals | Other: Placebo<br>* Placebo<br>|
| Experimental: Cohort 2, High Dose, PRV-101<br>High dose of PRV-101 by intramuscular injection, 3 doses at 4-week intervals | Biological: PRV-101<br>* Coxsackie Virus B vaccine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (safety and tolerability) | Adverse events will be assessed by frequency and criteria for severity (mild, moderate or severe) | Throughout the 32 weeks of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of neutralizing antibodies to coxsackie B virus (immunogenicity, efficacy) | Proportion of responders (ie, those that seroconvert or have at least a 4-fold increase in neutralizing antibody titers to any of the coxsackie B virus strains as measured by plaque reduction assay using serial serum dilutions) | Days 1, 29, and 57 and Weeks 12 and 32 | 
| Titer of antibodies to coxsackie B virus (immunogenicity, efficacy) | Mean and peak geometric mean serum IgG titers of antibodies against any of the coxsackie B virus strains, measured by ELISA | Days 1, 29 and 57 and weeks 12 and 32 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coxsackie Virus B, vaccine