Safety and Immunogenicity of Venezuelan Equine Encephalomyelitis Vaccine in Healthy Adults (VEE)

Phase 2 Open-Label Safety and Immunogenicity Study of the Venezuelan Equine Encephalomyelitis (VEE) Vaccine, Live Attenuated, Dried, TC-83, NDBR 102, Lot 4, Run 3, as Primary Vaccination in Healthy Adult Subjects at Risk of Exposure to VEE Virus

The purpose of this study is to evaluate the safety and immunogenicity of VEE vaccine, Live, Attenuated, dried TC-83, NDBR 102, Lot 4, Run 3, and collect data on the incidence of occupational VEE virus infection in vaccinated personnel.

Study Overview

• Status: Active, not recruiting
• Conditions: Venezuelan Equine Encephalomyelitis Virus Disease
• Intervention / Treatment: Biological: VEE Vaccine

Detailed Description

This protocol is replacing NCT00582504.

The study population will consist of USAMRIID and qualified extramural participants who are at risk of exposure to VEE virus. This study will be performed at the USAMRIID SIP Clinic. This open-label study represents a continuation of previous research conducted at USAMRIID. Subjects will be vaccinated with 0.5 mL of VEE vaccine, Live, Attenuated TC-83, NDBR 102, Lot 4, Run 3 subcutaneously in the upper outer aspect of the triceps region. Subjects will contacted the following day and weekly for 4 weeks to assess for adverse events.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Fort Deterick, Maryland, United States, 21702
      • Special Immunizations Program, Division of Medicine, USAMRIID

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be 18-65 years old at time of consent.
2. Have VEE virus PRNT80 < 1:10.
3. If female of childbearing potential, must agree to have a serum pregnancy test on the same day before vaccine administration. (Exception: documented hysterectomy or ≥ 3 years of menopause.) The results must be negative. Females must agree not to become pregnant for 3 months after receipt of the vaccination.
4. Be considered at risk for exposure to VEE virus and who have submitted a Request for IND Vaccines for the VEE vaccine.
5. Sign and date the approved informed consent document and HIPAA Authorization.

6. Have in their charts:

   • medical history (including concomitant medications) within 60 days of planned first administration of vaccine
   • physical examination and laboratory tests within 1 year
   • previous chest radiograph results and electrocardiogram
7. Be medically cleared for participation by an investigator. Examinations or tests may be repeated at the discretion of the PI.
8. Be willing to return for all follow-up visits.
9. Agree to report any AEs that may or may not be associated with administration of the vaccine for at least 28 days after administration and agree to report all SAEs (for example, resulting in hospitalization) for the duration of the subject's participation in the study.
10. Agree to defer blood donation for 1 year after receipt of the vaccine.

Exclusion Criteria:

1. Have received VEE vaccine.
2. Have family history (first degree relative) of diabetes mellitus (any type), a personal or family history of gestational diabetes, a confirmed elevated fasting serum glucose test (> 125 mg/dL), or a hemoglobin A1c > 5.6%. (At the principal investigator's discretion, a subject may participate if the family history of diabetes is only of late onset in an elderly parent.)
3. Have clinically significant abnormal laboratory results (including evidence of hepatitis C, hepatitis B carrier state) or elevated liver function tests (two times the normal range or at the discretion of the PI).
4. Have a personal history of an immunodeficiency or received treatment with an immunosuppressive medication, such as systemically administered glucocorticoids (eg prednisone) within 1 month before planned administration of the vaccine or with other immunosuppressive therapies within 6 months of planned administration of the vaccine. Other immunosuppressive therapies include all cancer chemotherapeutic agents, drugs to prevent transplant rejection, interferons, monoclonal antibodies, protein kinase inhibitors, methotrexate, TNF (tumor necrosis factor) inhibitors, and any other drug determined to be immunosuppressive by the PI. Current administration of topical, inhalational, or intranasal glucocorticoids is not excluded.
5. Have confirmed HIV infection (antibody positivity).
6. Have a positive pregnancy test or a breastfeeding female.

7. Have any known allergies to components of the vaccine:

   • Neomycin sulfate
   • Guinea pig heart cells
   • Streptomycin
   • Human serum albumin
8. History of serious allergic reaction to guinea pigs or guinea pig products. (Subjects who have known allergies to guinea pigs will be evaluated. The vast majority of individuals who are allergic to guinea pigs are allergic to the dander from the animals. An individual with a past serious allergic reaction to guinea pigs will be excluded.)
9. Have administration of another vaccine or investigational product within 28 days of VEE vaccination.
10. Have any unresolved AE resulting from a previous immunization.
11. Have a medical condition that, in the judgment of the PI, would impact subject safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VEE Vaccine; 0.5 mL of VEE vaccine, Live, Attenuated TC-83, NDBR 102, Lot 4, Run 3	Biological: VEE Vaccine; 0.5 mL of VEE vaccine administered subcutaneously in the upper outer aspect of the triceps region.; Other Names: TC-83

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Occurrence of Serious Adverse Events and Adverse Events (SAEs and AEs)	Collect and assess safety data for VEE vaccine	15 months
Safety: Percentage of subjects with symptoms following VEE vaccination	Collect and assess safety data for VEE vaccine	15 months
Safety: Percentage of subjects with each AE, system organ class of AE, severity, and association with vaccination	Collect and assess safety data for VEE vaccine	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity: Percentage of subjects who develop titers of >1:20	Percentage of subjects who develop titers of ≥ 1:20 as determined by PRNT80 after VEE vaccination at each scheduled time point for which blood samples are taken and over the entire study period to study completion.	15 months
Immunogenicity: Geometric Mean PRNT80 Titers of subjects	Geometric mean PRNT80 titers of subjects at each scheduled time point for which blood samples are taken and over the entire study period to study completion.	15 months

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: US Army Medical Research Institute of Infectious Diseases
• Investigators: Principal Investigator: Ronald B. Reisler, MD, MPH, USAMRIID

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2018
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Encephalitis; Alphavirus Infections; Togaviridae Infections; Virus Diseases; Encephalomyelitis; Encephalomyelitis, Equine; Encephalomyelitis, Venezuelan Equine
• Other Study ID Numbers: S-13-04; IND 142 (Other Identifier: Food and Drug Administration); M-10510 (Other Identifier: IRB); FY15-12 (Other Identifier: USAMRIID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No