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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Tuberculosis; Tuberculosis Vaccines

Treatments: Biological: GSK Biologicals' investigational TB vaccine (GSK692342); Biological: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01755598

115616

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3,575 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3,575 participants in 2 patient groups, including a placebo group

M72AS01 Group

Experimental group

Description:

Subjects, between, and including, 18 and 50 years of age, who received 2 doses of M72/AS01E according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.

Treatment:

Biological: GSK Biologicals' investigational TB vaccine (GSK692342)

Control group

Placebo Comparator group

Description:

Subjects, between, and including,18 and 50 years of age, who received 2 doses of Placebo according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.

Treatment:

Biological: Placebo