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

HIV Infections Clinical Trial

Official title:

DARDAR Health Project (Disseminated Tuberculosis and HIV Infection)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00052195
• Other study ID #: 1R01AI045407-01A2
• Secondary ID: 1R01AI045407-01A
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 24, 2003
• Last updated: February 17, 2016
• Start date: September 2001
• Est. completion date: May 2009

Study information

• Verified date: February 2016
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1975
• Est. completion date: May 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Tuberculosis

Intervention

Biological:
• SRL-172
5 doses of 0.1mL vaccine or placebo given intradermally over 12-months

Locations

Country	Name	City	State
Tanzania	Muhimbili University College of Health Sciences	Dar es Salaam

Sponsors (2)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Tanzania, 

References & Publications (3)

Lahey T, Arbeit RD, Bakari M, Horsburgh CR, Matee M, Waddell R, Mtei L, Vuola JM, Pallangyo K, von Reyn CF. Immunogenicity of a protective whole cell mycobacterial vaccine in HIV-infected adults: a phase III study in Tanzania. Vaccine. 2010 Nov 10;28(48): — View Citation

Mtei L, Matee M, Herfort O, Bakari M, Horsburgh CR, Waddell R, Cole BF, Vuola JM, Tvaroha S, Kreiswirth B, Pallangyo K, von Reyn CF. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis. 2 — View Citation

von Reyn CF, Mtei L, Arbeit RD, Waddell R, Cole B, Mackenzie T, Matee M, Bakari M, Tvaroha S, Adams LV, Horsburgh CR, Pallangyo K; DarDar Study Group. Prevention of tuberculosis in Bacille Calmette-Guérin-primed, HIV-infected adults boosted with an inacti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB		every six months	Yes
Secondary	Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis		every six months	No