Study to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by GlaxoSmithKline
Sponsor:
Collaborator:
Aeras
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01755598
First received: December 19, 2012
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to evaluate the protective efficacy of two doses of GSK Biologicals' candidate TB vaccine against pulmonary TB, as compared to placebo. The efficacy will be evaluated in adults living in TB endemic countries and aged 18 - 50 years because pulmonary TB occurs frequently in these countries and age range. In addition, the safety and immunogenicity of the candidate tuberculosis vaccine will be evaluated in a subset of volunteers.


Condition Intervention Phase
Tuberculosis
Biological: GSK Biologicals' investigational TB vaccine (GSK692342)
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy of GSK Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342 Against TB Disease, in Adults Living in a TB Endemic Region

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incident cases of definite pulmonary TB disease not associated with HIV-infection meeting the first case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incident cases of definite Xpert MTB/RIF pulmonary TB disease not associated with HIV-infection, meeting the second case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ] [ Designated as safety issue: No ]
  • Incident cases of definite pulmonary TB disease meeting the third case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ] [ Designated as safety issue: No ]
  • Incident cases of Microbiological Pulmonary TB disease meeting the fourth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ] [ Designated as safety issue: No ]
  • Incident cases of clinical TB disease meeting the fifth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ] [ Designated as safety issue: No ]
  • Occurrence of serious adverse events. [ Time Frame: During the entire study period (Day 0 to Month 36). ] [ Designated as safety issue: No ]
  • Occurrence of unsolicited adverse events. [ Time Frame: During the 30 day follow-up period following vaccination (day of vaccination and 29 subsequent days after each vaccine dose). ] [ Designated as safety issue: No ]
  • Occurrence of solicited local and general adverse events in the safety and immune sub-cohort. [ Time Frame: During the 7 day follow-up period following vaccination (day of vaccination and 6 subsequent days after each vaccine dose). ] [ Designated as safety issue: No ]
  • Occurrence of all potential immune-mediated diseases (pIMDs). [ Time Frame: Over a period starting at Day 0 until 6 months post dose 2 (Month 7). ] [ Designated as safety issue: No ]
  • Evaluation of Cell-mediated Immune (CMI) responses in the safety and immune sub-cohort in terms of frequency of M72-specific CD4+/CD8+ T cells expressing TNF-α and/or IFN-γ and/or IL-2 and/or CD40L per million cells identified after in vitro stimulation. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ] [ Designated as safety issue: No ]
  • Evaluation of humoral responses with respect to components of the study vaccine, in the safety and immune sub-cohort in terms of M72-specific antibody titres and seropositivity rates as measured by ELISA. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ] [ Designated as safety issue: No ]
  • Occurrence of grade ≥ 2 haematological and biochemical levels in the safety and immune sub-cohort. [ Time Frame: Days 0, 7, 30 and 37. ] [ Designated as safety issue: No ]

Estimated Enrollment: 3506
Study Start Date: August 2014
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine group
Subjects will receive 2 doses of the candidate tuberculosis vaccine (Day 0 and Day 30).
Biological: GSK Biologicals' investigational TB vaccine (GSK692342)
2 doses administered intramuscularly in the deltoid region of the arm.
Placebo Comparator: Control group
Subjects will receive 2 doses of placebo (Day 0 and Day 30).
Biological: Placebo
2 doses administered intramuscularly in the deltoid region of the arm.

Detailed Description:

Case Definitions:

• First case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.

• Second case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and confirmed HIV-negative at the time of TB diagnosis.

• Third case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.

• Fourth case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture.

• Fifth case definition: A subject for whom a clinician has diagnosed TB disease and has decided to treat the patient with TB treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who, in the opinion of the investigator, 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 obtaining informed consent.
  • Written (or thumb printed and witnessed) informed consent obtained from the subject.
  • Baseline positive IGRA test result.
  • Baseline negative HIV screen.
  • Baseline negative clinical screening questionnaire and negative sputum sample for Pulmonary TB disease.
  • Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination.
  • Female subjects of non-childbearing potential may be enrolled in the study.

    • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
  • Female subjects of childbearing potential may be enrolled in the study, if the subject:

    • has practiced adequate contraception for 25 days prior to vaccination, and
    • has a negative pregnancy test on the day of screening and the day of first vaccination, and
    • has agreed to continue adequate contraception during the entire vaccination period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

  • Current TB disease or history of TB disease and/or treatment for TB.
  • Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after each dose of vaccine.
  • History of previous administration of experimental Mtb vaccines.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. 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.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Planned participation or participation in another experimental protocol during the study.
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • History of medically confirmed autoimmune disease.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination period and/or before 2 months after completion of the vaccination series.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755598

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
South Africa
GSK Investigational Site Not yet recruiting
Klerksdorp, North-West, South Africa, 2571
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Bellville, South Africa, 7530
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Pretoria, South Africa
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Aeras
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01755598     History of Changes
Other Study ID Numbers: 115616
Study First Received: December 19, 2012
Last Updated: September 11, 2014
Health Authority: South Africa: Medicines Control Council

Keywords provided by GlaxoSmithKline:
Positive Interferon-γ release assay
Efficacy
Adults
Tuberculosis vaccine
Endemic region

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on September 18, 2014