Clinical trial NCT00707967: Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in HIV-positive Adults.
Official title: Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine (692342) in HIV-positive Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-01
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will assess the safety and immunogenicity of a GSK Biologicals' candidate TB vaccine (692342) administered at 0, 1 month to HIV-positive adults living in Switzerland.


Eligibility criteria: Inclusion Criteria:

* Subjects who the Investigator believes that they can and will comply with the requirements of the protocol.
* A male or female between, and including, 18 and 50 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject prior to any study procedure.
* Subjects must be HIV-positive and must have:

  * received Highly Active Antiretroviral therapy for a minimum of 12 consecutive months prior to screening
  * documented suppressed HIV-1 RNA levels following HAART-treatment.
  * a protocol defined CD4+ T cell count at screening
* If the subject is female, she must be of non-childbearing potential, or she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of vaccination.
* Clinically acceptable laboratory values prior to randomisation as determined by the Investigator.
* No evidence of TB disease with no pulmonary pathology as confirmed by chest X-ray.
* No history of extrapulmonary TB.
* No history of chemotherapy for TB.

Exclusion Criteria:

* Any change in antiretroviral drug regimen within 12 weeks prior to screening.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Administration of a registered live vaccine not foreseen by the study within 30 days preceding the first dose of study vaccine and administration of a registered inactivated vaccine within 14 days preceding the first dose of study vaccine.
* History of previous administration of experimental Mycobacterium tuberculosis vaccines.
* History of previous exposure to experimental products containing components of the experimental vaccine.
* Chronic administration of immunosuppressive or other immune-modifying drugs within six months prior to the first vaccine dose.
* Administration of any immunoglobulins, any immunotherapy and/or any blood products within the three months preceding the first dose of study vaccination, or planned administrations during the study period.
* Any condition or illness (acute, chronic or history) or medication, which in the opinion of the Investigator might interfere with the evaluation of the safety or immunogenicity of the vaccine.
* Planned participation or participation in another experimental protocol during the study period.
* A family history of congenital or hereditary immunodeficiency. •Any chronic drug therapy, other than HAART or prophylaxis for opportunistic HIV-related infections to be continued during the study period. Vitamins and/or dietary supplements, birth control pills, anti-histamines for seasonal allergies and SSRIs are allowed.
* Subjects taking any of the following medication: systemic steroids, interleukins, systemic interferons or systemic chemotherapy.
* History of allergic reactions or anaphylaxis to any vaccine.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* History of chronic alcohol consumption and/or drug abuse which in the Investigator's opinion would put the subject at risk.
* Pregnant female, lactating female or female planning to become pregnant or stop contraception.

Primary outcomes:
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7-day period (Days 0-6) post vaccination following each dose
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7-day period (Days 0-6) post vaccination following each dose
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day period (Days 0-29) post vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period, from Day 0 up to Day 210
measure: Number of Subjects With Normal Biochemical and Haematological Levels
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Normal Haematological Levels
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Normal Haematological Levels
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Biochemical and Haematological Levels Below Normal
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Haematological Levels Below Normal
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Haematological Levels Below Normal
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Biochemical and Haematological Levels Above Normal
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Haematological Levels Above Normal
timeFrame: At Day 0, 7, 30, 37 and 60
measure: Number of Subjects With Haematological Levels Above Normal
timeFrame: At Day 0, 7, 30, 37 and 60
Secondary outcomes:
measure: Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines
timeFrame: At Day 0, 30, 60 and 210
measure: Frequency of M72 Specific CD4/8+ T Cells Expressing at Least One Cytokine and Another Signal Molecule
timeFrame: At Day 0, 30, 60 and 210
measure: Cell Count of CD4+ T Cells
timeFrame: At Day 0, 30, 60 and 210
measure: Anti-M72 Specific Antibody Concentrations
timeFrame: At Day 0, 30, 60 and 210
measure: Number of Subjects With Significant Highly Active Anti-Retroviral Therapy (HAART) Changes
timeFrame: From Day 60 to Day 210
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Thacher EG, Cavassini M, Audran R, Thierry AC, Bollaerts A, Cohen J, Demoitie MA, Ejigu D, Mettens P, Moris P, Ofori-Anyinam O, Spertini F. Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial. AIDS. 2014 Jul 31;28(12):1769-81. doi: 10.1097/QAD.0000000000000343.
citation: Roy-Ghanta S, Van der Most R, Li P, Vaughn DW. Responses to A(H1N1)pdm09 influenza vaccines in participants previously vaccinated with seasonal influenza vaccine: a randomized, observer-blind, controlled study. J Infect Dis. 2014 Nov 1;210(9):1419-30. doi: 10.1093/infdis/jiu284. Epub 2014 May 26.