Safety and Immunogenicity Study of a Live Francisella Tularensis Vaccine

• ClinicalTrials.gov Identifier: NCT00584844
• Recruitment Status: Completed
• First Posted: January 2, 2008
• Results First Posted: July 2, 2017
• Last Update Posted: January 2, 2020
• Sponsor: U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): U.S. Army Medical Research and Development Command

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Tularemia	Biological: Live F tularensis Vaccine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 484 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Longitudinal Phase 2 Study for the Continued Evaluation of the Safety and Immunogenicity of a Live Francisella Tularensis Vaccine, NDBR 101, Lot 4
• Study Start Date: October 2004
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: October 2013

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Immunogenicity: Protocol Compliant Post-primary Titer Rates [ Time Frame: 12 months ]
   Percentage of subjects with less than or greater than titers (> or < 1:20) for compliant post-primary titers.
2. Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates [ Time Frame: 12 months ]
   Percentage of subjects with less than or greater than titers (> or < 1:20) who received post-boost 1
3. Immunogenicity: Protocol-compliant Post-boost 2 Titer [ Time Frame: 12 months ]

   Percentage of subjects with less than or greater than titers who received post-boost 2.

   Responder = > 1:20 Non-responder = < 1:20

Eligibility Criteria

• Ages Eligible for Study: 17 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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. >

Contacts and Locations

Locations

United States, Maryland

U.S. Army Medical Research Institute of Infectious Diseases

Fort Deterick, Maryland, United States, 21702

Sponsors and Collaborators

U.S. Army Medical Research and Development Command

Investigators

• Principal Investigator: Mark Goldberg, MD; USAMRIID Medical Division

More Information

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00584844
• Other Study ID Numbers: A-12775; FY03-24 ( Other Identifier: SIP )
• First Posted: January 2, 2008
• Results First Posted: July 2, 2017
• Last Update Posted: January 2, 2020
• Last Verified: December 2019

Keywords provided by U.S. Army Medical Research and Development Command:

Live Vaccine Strain (LVS), Bacterial Infections, Ulceroglandular, Oculoglandular

Additional relevant MeSH terms:

Tularemia; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tick-Borne Diseases; Vector Borne Diseases