Safety and Immunogenicity Study of a Live Francisella Tularensis Vaccine

A Longitudinal Phase 2 Study for the Continued Evaluation of the Safety and Immunogenicity of a Live Francisella Tularensis Vaccine, NDBR 101, Lot 4

This study is designed to determine the safety and immunogenicity of a Live Francisella tularensis Vaccine

Study Overview

• Status: Completed
• Conditions: Tularemia
• Intervention / Treatment: Biological: Live F tularensis Vaccine

Detailed Description

Study was designed as a continuation of previously published research and targets subjects who were at risk of occupational exposure to F tularensis virus. Based on screening examinations; if a subject had a positive baseline titer (<1:20) and gave no history of significant exposure to F tularensis or history of tularemia disease, had never received tularemia vaccination, and was at risk of exposure to F tularensis they could be enrolled in this protocol to receive vaccination. Subjects returned for follow-up exams on Days 1, 2, and 7; once between Days 12 and 16; and once between Days 28 and 35 post-vaccination. If titers; after blood samples on Days 28, 35 and 12 months showed <1:20 the vaccination could be repeated at Days 56-84. If the repeat titer remained <1:20, a booster vaccination could be administered. Subjects could be boosted 2 times with 1 year. If the titer measured 12 months after vaccination (+30 days) was >1:20 and the subject had no lingering AEs, the subjects participation was considered complete.

• Study Type: Interventional
• Enrollment (Actual): 484
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Fort Deterick, Maryland, United States, 21702
      • U.S. Army Medical Research Institute of Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:>

• At least 18 years old, or if on active military duty, 17 years old >
• Females of childbearing potential must agree to have a urine pregnancy test immediately before vaccination (Exception: documented hysterectomy or > 3 years of menopause). The results must be negative. Volunteers must agree not to become pregnant for 3 months after receipt of the vaccine.>
• Subject must be actively enrolled in the SIP >
• Subjects must be considered at risk for exposure to F. tularensis.>
• Subjects must have an up-to-date (within 1 year) medical history, physical examination, and laboratory tests on their charts and be medically cleared for participation by an investigator. Examinations or tests may be repeated within 1 year at the discretion of the enrolling physician.>
• Volunteer must be willing to return for all follow-up visits on days 1, 2, 7, once between days 12-16, and once between days 28-35, days 56-84 (if needed), all visits for serology, as well as an annual visit while enrolled in protocol.>
• Volunteer must agree to report any Adverse Event which may or may not be associated with administration of the test article for at least 28 days after vaccination. All Serious and Unexpected Adverse Events will be reported for the duration of the volunteer's participation in the study. >

Exclusion Criteria:>

• Clinically significant abnormal lab results including evidence of Hepatitis C*, Hepatitis B* carrier state, or elevated liver function tests (2X normal values or at discretion of PI).>
• Personal history of an immunodeficiency or current treatment with an oral or intravenous immunosuppressive medication.>
• Confirmed HIV* infection.>
• Any other medical condition at the discretion of the PI.>
• Antibiotic therapy for 7 days before vaccination.>
• Females must not be pregnant or lactating (females must agree to not become pregnant for 3 months after vaccination).>
• Any known allergies to excipients of the vaccine>
• Administration of another live vaccine within 4 weeks or an inactivated vaccine (generally) within 7 days of tularemia vaccination.>
• Any unresolved adverse event resulting from a previous immunization. >

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: F tularensis Vaccine (0.0025 mL); Subjects receive a small amount of F tularensis vaccine (0.0025mL) placed on a cleansed site on the skin on the volar surface of the forearm. A bifurcated needle was used to make 15 superficial punctures at the vaccination site to permit percutaneous penetration of the vaccine.	Biological: Live F tularensis Vaccine; Subjects will receive one drop of reconstituted F tularensis vaccine (approximately 0.0025 ml), applied with a bifurcated needle to the volar surface of the forearm, and the skin will be pricked 15 times over the prepared area. A booster dose will be given at the same dose volume and route of administration if the titer (days 56-84) is inadequate (< 1:20).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Adverse Event Category Rates for All Vaccinations	AE analysis was conducted for all intent-to-treat subjects regardless of compliance with titer schedule.	AEs/SAEs recorded through duration of study; immunogenicity via MA on days 0, 28-35, 56-84, and at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity: Protocol Compliant Post-primary Titer Rates	Percentage of subjects with less than or greater than titers (> or < 1:20) for compliant post-primary titers.	12 months
Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates	Percentage of subjects with less than or greater than titers (> or < 1:20) who received post-boost 1	12 months
Immunogenicity: Protocol-compliant Post-boost 2 Titer	Percentage of subjects with less than or greater than titers who received post-boost 2. Responder = > 1:20 Non-responder = < 1:20	12 months

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 30, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Live Vaccine Strain (LVS), Bacterial Infections, Ulceroglandular, Oculoglandular
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Tick-Borne Diseases; Tularemia
• Other Study ID Numbers: A-12775; FY03-24 (Other Identifier: SIP)