Safety, Reactogenicity and Immunogenicity of a Venezuelan Equine Encephalitis DNA Vaccine Candidate Administered by Jet Injection

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the safety and reactogenicity of a VEE DNA Vaccine candidate delivered by either intramuscular or intradermal jet injection. The main question it aims to answer is: • Is the VEE DNA Vaccine candidate safe Participants will: Receive the VEE DNA Vaccine candidate by either intramuscular or intradermal jet injection Provide blood and urine samples Complete ECGs Complete physical exams Complete diaries

Official Title
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A Phase I, Randomized, Observer-Blind Trial to Assess the Safety, Reactogenicity and Immunogenicity of a Venezuelan Equine Encephalitis (VEE) DNA Vaccine Candidate Administered Intramuscularly and Intradermally by Jet Injection to Healthy Adults

Conditions
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Vaccine Reaction

Intervention / Treatment
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* Drug: Venezuelan Equine Encephalitis DNA Vaccine
* Device: PharmaJet Stratis Needle-free Injection System
* Device: PharmaJet Tropis Needle-free Injection System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults, male or female. Ages at least 18 at the start of the study and no greater than 49 years of age on Day 1 of vaccination. Participants must be available for all visits and for the complete duration of the study. Participants must, in the opinion of the Investigator or person obtaining consent, understand the information provided and be capable of providing informed consent. Women of child bearing potential (WOCBP) must have a negative pregnancy test and be willing to use an effective method of contraception: oral contraception, diaphragm, cervical cap, intrauterine device, condom, or be anatomically sterile (in self or partner) from the date of screening until at least 6 months after the last vaccination. If subject is a sexually active male, must be willing to use an effective method of contraception (such as condoms or be anatomically sterile) from screening until 6 months after the last vaccination. Exclusion Criteria: Clinically relevant abnormality on history or examination including a history of immunodeficiency or use of systemic corticosteroids, immunosuppressive, anticancer, or other medications considered to be significant by the designated trial physician in the last 6 months. Any acute or chronic medical condition requiring care of a physician (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the Investigator, would preclude participation. Any of the following laboratory parameters with abnormal values that are moderate in severity: hematology (hemoglobin, absolute neutrophil count, absolute lymphocyte count, platelets); urinalysis; biochemistries (total bilirubin, creatinine, AST, ALT). If female, pregnant, lactating, or planning pregnancy within 6 months of the final vaccination. Receipt of a blood transfusion or blood products 6 months prior to enrollment. Participation in another clinical trial of an investigational product currently or within the past 12 weeks or expected participation during the study. History of severe local or systemic reactions to vaccination or a history of severe allergic reactions. History of Guillain-Barre syndrome. Confirmed diagnosis of HBV infection (surface antigen positive, HBsAg); Hepatitis C infection (HCV Ab positive); HIV infection, or active syphilis. History of grand mal epilepsy, or currently taking anti-epileptics. Any condition associated with prolonged bleeding time, which would contraindicate skin or muscle injection. Abnormal ECG finding that, in the opinion of the Investigator, excludes the subject from participating. History of syncope or history of a fainting episode within one year of study entry. Extensive tattoos or markings covering the eligible sites of administration (the skin or muscle of the upper left and right deltoid muscles). Presence of any surgical/traumatic metal implants, or significant scar tissue that may impair appropriate injection at the eligible sites of administration (skin or muscle of the upper left and right deltoid muscles). In the opinion of the Investigator, is unlikely to comply with the protocol. As confirmed/reported by the study subject, a history of: exposure to Venezuelan Equine Encephalitis Virus (VEEV) or related alphavirus; prior immunization with an alphavirus replicon-based vaccine; prior immunization with a live-attenuated alphavirus vaccine; prior immunization with an inactivated alphavirus vaccine. A history of encephalitis as confirmed/reported by the study subject. Prior immunization against VEEV or related alphavirus or encephalitis, as confirmed/reported by the study subject. History of alcohol abuse, illicit drug use, physical dependence on any opioid, or any history of drug abuse (excluding marijuana) or addiction within 12 months of screening. Involved in the planning or conduct of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Intramuscular<br>Route (device): Intramuscular (PharmaJet Stratis Needle-free Injection System) Vaccine dose schedule (week): 0, 4, 8 Saline dose schedule (week): 26 | Drug: Venezuelan Equine Encephalitis DNA Vaccine<br>* Venezuelan Equine Encephalitis DNA Vaccine Candidate<br>Device: PharmaJet Stratis Needle-free Injection System<br>* Intramuscular Needle-free Injection System (Jet Injector)<br>|
| Experimental: 2: Intramuscular<br>Route (device): Intramuscular (PharmaJet Stratis Needle-free Injection System) Vaccine dose schedule (week): 0, 8, 26 Saline dose schedule (week): 4 | Drug: Venezuelan Equine Encephalitis DNA Vaccine<br>* Venezuelan Equine Encephalitis DNA Vaccine Candidate<br>Device: PharmaJet Stratis Needle-free Injection System<br>* Intramuscular Needle-free Injection System (Jet Injector)<br>|
| Experimental: 3: Intradermal<br>Route (device): Intradermal (PharmaJet Tropis Needle-free Injection System) Vaccine dose schedule (week): 0, 4, 8 Saline dose schedule (week): 26 | Drug: Venezuelan Equine Encephalitis DNA Vaccine<br>* Venezuelan Equine Encephalitis DNA Vaccine Candidate<br>Device: PharmaJet Tropis Needle-free Injection System<br>* Intradermal Needle-free Injection System (Jet Injector)<br>|
| Experimental: 4: Intradermal<br>Route (device): Intradermal (PharmaJet Tropis Needle-free Injection System) Vaccine dose schedule (week): 0, 8, 26 Saline dose schedule (week): 4 | Drug: Venezuelan Equine Encephalitis DNA Vaccine<br>* Venezuelan Equine Encephalitis DNA Vaccine Candidate<br>Device: PharmaJet Tropis Needle-free Injection System<br>* Intradermal Needle-free Injection System (Jet Injector)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate reactions | The nature, frequency, and severity of immediate reactions following vaccination | 30 minutes after each vaccination | 
| Solicited adverse events | The nature, frequency, and severity of solicited adverse events | 7 days after each vaccination | 
| Unsolicited adverse events | The nature, frequency, and severity of unsolicited adverse events | 28 days after the final vaccination | 
| Adverse events | The nature, frequency, and severity of adverse events | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VEEV-specific antibody | PsVNA50 | 1 year | 
| Seroconversion rate | PsVNA50 | 1 year |