Overview

This trial has been completed.

Condition tuberculosis
Treatments gsk's investigational vaccine 692342, physiological saline
Phase phase 2
Sponsor GlaxoSmithKline
Start date January 2011
End date July 2012
Trial size 240 participants
Trial identifier NCT01262976, 113935

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Experimental)
HIV-positive subjects on highly active anti retroviral therapy will receive GlaxoSmithKline's (GSK's) investigational vaccine 692342.
gsk's investigational vaccine 692342
Intramuscular, 2 doses
(Placebo Comparator)
HIV-positive subjects on highly active anti retroviral therapy will receive physiological saline.
physiological saline
Intramuscular, 2 doses
(Experimental)
Treatment naïve HIV-positive subjects will receive GSK's investigational vaccine 692342.
gsk's investigational vaccine 692342
Intramuscular, 2 doses
(Placebo Comparator)
Treatment naïve HIV-positive subjects will receive physiological saline.
physiological saline
Intramuscular, 2 doses
(Experimental)
HIV negative subjects will receive GSK's investigational vaccine 692342.
gsk's investigational vaccine 692342
Intramuscular, 2 doses
(Placebo Comparator)
HIV negative subjects will receive physiological saline.
physiological saline
Intramuscular, 2 doses

Primary Outcomes

Measure
Number of subjects with grade 3 solicited local symptoms
time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of subjects with grade 3 solicited general symptoms
time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of subjects with grade 3 unsolicited adverse events (AEs)
time frame: During the 30-day (Days 0-29) post-vaccination period
Number of subjects with serious adverse events (SAEs)
time frame: From screening up to one month post Dose 2
Number of subjects with grade 3 and grade 4 haematological and biochemical levels
time frame: At Day 0
Number of subjects with grade 3 and grade 4 haematological and biochemical levels
time frame: At Day 7
Number of subjects with grade 3 and grade 4 haematological and biochemical levels
time frame: At Day 30
Number of subjects with grade 3 and grade 4 haematological and biochemical levels
time frame: At Day 37
Number of subjects with grade 3 and grade 4 haematological and biochemical levels
time frame: At Day 60

Secondary Outcomes

Measure
Anti-Mycobacterium tuberculosis fusion protein (M72) specific antibody concentrations
time frame: At Day 0, 30, 60, 210 and Year 1
Number of seroconverted subjects for M72-specific antibodies
time frame: At Day 0, 30, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 4 (CD4+) T cells expressing at least 2 immune markers
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 4 (CD4+) T cells expressing any combination of cytokines
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 4 (CD4+) T cells expressing any combination of cytokines
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 8 (CD8+) T cells expressing at least 2 immune markers
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 8 (CD8+) T cells expressing any combination of cytokines
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Frequency of M72-cluster of differentiation 8 (CD8+) T cells expressing any combination of cytokines
time frame: At Day 0, 7, 30, 37, 60, 210 and Year 1
Number of subjects with any solicited local symptoms
time frame: During the 7-Day (Days 0-6) post-vaccination period following each dose and across doses
Number of subjects with any solicited general symptoms
time frame: During the 7-Day (Days 0-6) post-vaccination period following each dose and across doses
Number of subjects with any unsolicited AEs
time frame: During the 30-Day (Days 0-29) post-vaccination period
Number of subjects with SAEs
time frame: From one month post Dose 2 up to Year 1
Number of subjects presenting different grades of haematological and biochemical values
time frame: At Day 0, 7, 30, 37 and 60
Number of subjects presenting different grades of haematological and biochemical values
time frame: At Day 0, 7, 30, 37 and 60

Eligibility Criteria

Male or female participants from 18 years up to 59 years old.

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.

Additional Information

Official title Safety and Immunogenicity of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to HIV-positive Adults Living in a Tuberculosis Endemic Region
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.