Investigational Vaccine for the Prevention of Disseminated Tuberculosis in HIV Infected People

Phase 2

Completed

• Conditions: HIV Infections; Tuberculosis
• Interventions: Biological: SRL-172

• Registration Number: NCT00052195
• Lead Sponsor: Dartmouth-Hitchcock Medical Center

Brief Summary

A significant number of HIV infected patients in Africa also have disseminated tuberculosis (infection throughout multiple organs). This type of tuberculosis is a significant cause of mortality in these patients. The purpose of this study is to evaluate the safety and effectiveness of a vaccine designed to prevent disseminated tuberculosis.

Detailed Description

Disseminated infection with Mycobacterium tuberculosis (dMTB) has been documented in 10% to 25% of patients with HIV infection in Africa. Unlike pulmonary tuberculosis (pMTB), most cases of dMTB are not recognized and death ensues rapidly. Therefore, dMTB may be a more important cause of HIV-associated mortality than pMTB in developing countries. Mycobacterium vaccae (MV) is an investigational vaccine prepared by heat inactivation of a nontuberculous mycobacteria. MV immunization may reduce the risk of HIV-associated dMTB. The purpose of this study is to define risk factors for HIV-associated dMTB and to assess the safety and effectiveness of an MV vaccine for the prevention of HIV-associated pulmonary and disseminated tuberculosis.

HIV positive patients with prior BCG immunization and HIV negative controls will be entered in a 5-year study in Tanzania. Participants will be randomized to receive a 5-dose series of MV or placebo over 12 months, with a repeat skin test at Month 14. Baseline evaluation will include medical history, chest x-ray, skin tests with purified protein derivative (PPD), and blood tests to evaluate interferon-gamma production. Participants with PPD reactions greater than or equal to 5 mm will receive 6 months of prophylaxis with isoniazid. Participants will be followed every 3 months for 3 to 5 years to assess new pMTB (microbiologic or clinical diagnosis) or dMTB (microbiologic diagnosis). Potential risk factors for dMTB will also be assessed.

Study Timeline

• Study Start: 2001-09
• Study First Submitted: 2003-01-24
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2008-12
• Study Completion: 2009-05
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-17
• Last Update Posted: 2016-02-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1975

Inclusion Criteria

• HIV infection
• CD4 count more than 200 cells/mm3
• BCG scar

Exclusion Criteria

• Active tuberculosis. Patients will be deferred from study enrollment until they show no signs of active disease.
• Serious underlying disease (e.g., congestive heart failure, advanced cancer)
• Life expectancy of less than 2 years
• Pregnancy. Women who are pregnant may be eligible for the study after they give birth.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	SRL-172	-
B	SRL-172	-

Primary Outcome Measures

Name	Time	Method
safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB	every six months

Secondary Outcome Measures

Name	Time	Method
Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis	every six months

Trial Locations

Locations (1)

Muhimbili University College of Health Sciences; 🇹🇿 Dar es Salaam, Tanzania