Clinical trial NCT01424501: Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in Adults With TB Disease
Official title: Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342 When Administered to Adults With TB Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis vaccine
HIV-negative
tuberculosis treatment
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 142
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: This study will assess the safety and immunogenicity of GSK Biologicals' investigational tuberculosis (TB) vaccine (GSK 692342) compared to placebo when administered at 0, 1 months to human immunodeficiency virus (HIV) negative adults who have received treatment for TB disease (denoted TB-treated cohort) or are currently receiving treatment for TB disease (denoted TB-treatment cohort). For comparative purposes, subjects who have never had TB disease (denoted TB-naïve cohort) will also be enrolled.

Detailed description: A Protocol Amendment 1, May 2012, was made following the decision to add a second country in the study (i.e. Estonia).

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes 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.
* 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, and
  * 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.
* Seronegative for HIV- 1 and -2 antibodies.
* No history of or current extrapulmonary tuberculosis TB. Additionally, based on medical history,
* Subjects in the TB-naive cohort must

  * have no active pulmonary disease as indicated by chest X-ray.
  * have no signs and symptoms of TB.
  * have no history of chemoprophylaxis or treatment for TB.
* Subjects in the TB-treated cohort must

  * have a history of successful treatment for pulmonary TB (completed at least 1 year prior to vaccination).
  * have no active pulmonary disease on chest X-ray.
* Subjects in the TB-treatment cohort must - have documented treatment for pulmonary TB (smear- or culture confirmed) ongoing for 2-4 months prior to vaccination.

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.
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* Any chronic drug therapy to be continued during the study period, which in the opinion of the investigator could adversely interfere with the vaccine.
* History of previous administration of experimental TB vaccines.
* History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine.
* Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
* Planned participation or participation in another experimental protocol during the study period.
* Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
* History of chronic alcohol and/or drug abuse.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* Major congenital defects.
* Pregnant female, lactating female or female planning to become pregnant or discontinue contraceptive precautions during the active phase of the study (from study start till 2 months after dose 2).
* Additionally, for the TB naïve and TB treated cohorts:

  - Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests
* Additionally, for the TB treatment cohort:

  * Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests. Individuals with grade 3 levels will be excluded.
  * Failure to convert while on anti-TB treatment at the end of the second month of anti-TB therapy.

Primary outcomes:
measure: Number of Subjects With Any and 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 Any, Grade 3 and Related 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 Adverse Events (AEs)
timeFrame: During the 30 day (Days 0-29), after vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to day 210
Secondary outcomes:
measure: Number of Subjects With Anti-Mycobacterium Tuberculosis Fusion Protein M72 Antibodies
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Day 30), post-dose 2 (Days 60 and 210)
measure: Concentrations of Anti-M72 Antibodies
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Day 30), post-dose 2 (Days 60 and 210)
measure: Frequency of M72-specific Cluster of Differentiation 4 (CD4+) T-cells Expressing Any Combination of the Different Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD4+ T-cells Expressing at Least 2 Immune Markers Among 6
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Cytokines
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD4+ T-cells M72-specific Expressing Any Combination of Cytokines
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD4+ T-cells M72-specific Expressing Any Combination of Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD4+ T-cells Expressing Cytokines in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD4+ T-cells Expressing Immune Markers in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD4+ T-cells M72-specific Expressing Cytokines in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD4+ T-cells M72-specific Expressing Immune Markers in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific Cluster of Differentiation 8 (CD8+) T-cells Expressing at Least 2 Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD8+ T-cells Expressing at Least 2 Immune Markers Among 6
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD8+ T-cells Expressing Any Combination of Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD8+ T-cells Expressing Any Combination of Cytokines
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD8+ T-cells M72-specific Expressing Any Combination of Immune Markers
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD8+ T-cells M72-specific Expressing Any Combination of Cytokines
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD8+ T-cells Expressing Cytokines in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of M72-specific CD8+ T-cells Expressing Immune Markers in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD8+ T-cells M72-specific Expressing Cytokines in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
measure: Frequency of CD8+ T-cells M72-specific Expressing Immune Markers in Any Combination
timeFrame: Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)
Other outcomes:
Locations:
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan Hsien
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Coccia M, Burny W, Demoitie MA, Gillard P, van den Berg RA, van der Most R. Subsequent AS01-adjuvanted vaccinations induce similar transcriptional responses in populations with different disease statuses. PLoS One. 2022 Nov 10;17(11):e0276505. doi: 10.1371/journal.pone.0276505. eCollection 2022.
citation: Gillard P, Yang PC, Danilovits M, Su WJ, Cheng SL, Pehme L, Bollaerts A, Jongert E, Moris P, Ofori-Anyinam O, Demoitie MA, Castro M. Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study. Tuberculosis (Edinb). 2016 Sep;100:118-127. doi: 10.1016/j.tube.2016.07.005. Epub 2016 Jul 21.