Clinical trial NCT01262976: Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Human Immunodeficiency Virus (HIV)-Positive Adults
Official title: Safety and Immunogenicity of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to HIV-positive Adults Living in a Tuberculosis Endemic Region
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-12-20
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to assess the safety and immunogenicity of a GlaxoSmithKline (GSK) Biologicals' candidate tuberculosis vaccine (692342) administered to Human Immunodeficiency Virus (HIV)-positive adults aged 18 to 59 years, living in a tuberculosis endemic region.

Subjects will be followed-up for 3 years.

Subjects will be enrolled in 3 cohorts:

* HIV-positive adults on highly active antiretroviral therapy
* HIV-positive adults not on highly active antiretroviral therapy
* HIV-negative adults

Each cohort will have 2 groups.

Detailed description: This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the outcome measures and the inclusion and exclusion criteria.

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 59 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject prior to any study procedure.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination,
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
* Clinically acceptable laboratory values at screening as determined by the investigator.
* No evidence of tuberculosis disease with no evidence of pulmonary pathology as confirmed by chest X-ray.
* No history of extra pulmonary tuberculosis.
* Based on their medical history, all subjects must have no history of chemotherapy for tuberculosis.

Additional inclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:

* Subjects must be HIV-positive and under care of a physician for at least 6 months.
* Subjects must have a CD4+T cell count \>= 250 cells/mm3 at screening.
* Subjects must be stable on highly active antiretroviral therapy for at least 6 months, with an undetectable HIV viral load level at screening.

Additional inclusion criteria for subjects to be enrolled in HIV+ treatment naïve cohort:

* Subjects must be HIV-positive and under care of a physician for at least 6 months
* Subjects must be highly active antiretroviral therapy-naïve (never received anti-retroviral therapy after HIV diagnosis)
* Subjects must have a CD4 + T cell count above 350 cells/mm3 at screening.
* Subjects for whom commencement of highly active antiretroviral therapy is not expected based on current assessment within next year.
* Subjects must have a viral load between 5000 - 80000 copies/mL at screening.

Additional inclusion criteria for subjects to be enrolled in HIV-negative cohort

• Subjects must be negative for HIV-1.

Exclusion Criteria:

* Use of any investigational or non-registered product 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 Mtb vaccines.
* History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine
* Chronic administration of immunosuppressant or other immune-modifying drugs within six months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone \>= 20 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
* Any condition or illness 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 with an experimental product during the study period.
* Administration of any immunoglobulin, 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.
* Subjects taking any of the following medication: chronic administration of systemic steroids, interleukins, systemic interferon or systemic chemotherapy.
* History of allergic reactions or anaphylaxis to any drug or 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.
* Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests.

Additional exclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:

* Any change in anti-retroviral drug regimen within 12 weeks prior to screening.
* Any chronic drug therapy, other than highly active antiretroviral therapy or prophylaxis for opportunistic HIV related infections, birth control pills, anti-histamines for seasonal allergies and SSRIs.

Primary outcomes:
measure: Number of Subjects With Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Grade 3 Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From screening up to one month post Dose 2
measure: Number of Subjects With Grade 3 and Grade 4 Haematological and Biochemical Levels
timeFrame: At Day 0
measure: Number of Subjects With Grade 3 and 4 Haematological and Biochemical Levels
timeFrame: At Day 7
measure: Number of Subjects With Grade 3 and Grade 4 Haematological/Biochemical Levels
timeFrame: At Day 30
measure: Number of Subjects With Grade 3-4 Haematological and Biochemical Levels
timeFrame: At Day 37
measure: Number of Subjects With Grade 3-4 Haematological/Biochemical Levels
timeFrame: At Day 60
Secondary outcomes:
measure: Anti-Mycobacterium Tuberculosis Fusion Protein (M72) Specific Antibody Concentrations
timeFrame: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
measure: Number of Seroconverted Subjects for M72-specific Antibodies
timeFrame: At Days 0, 30, 60, 210 and at Years 1, 2 and 3
measure: Frequency of M72-cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Immune Markers
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: Frequency of M72-CD4+ T-cells Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: M72-cluster of Differentiation 4 (CD4+) T-cells Frequency Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: M72-CD4+ T-cells Frequency Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: Frequency of M72-cluster of Differentiation 8 (CD8+) T-cells Expressing at Least 2 Immune Markers
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: Frequency of M72-CD8+ T-cells Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: M72-cluster of Differentiation 8 (CD8+) T Frequency Cells Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: M72-CD8+ T-cells Frequency Expressing Any Combination of Cytokines
timeFrame: At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3
measure: Number of Subjects With Any Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any Unsolicited AEs
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With SAEs
timeFrame: From one month post Dose 2 up to study end (Year 3)
measure: Number of Subjects Presenting Different Grades of Haematological and Biochemical Values
timeFrame: At Days 0, 7, 30, 37 and 60
Other outcomes:
Locations:
city: Tharamani Chennai
country: India
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kumarasamy N, Poongulali S, Beulah FE, Akite EJ, Ayuk LN, Bollaerts A, Demoitie MA, Jongert E, Ofori-Anyinam O, Van Der Meeren O. Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial. Medicine (Baltimore). 2018 Nov;97(45):e13120. doi: 10.1097/MD.0000000000013120.