Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in Adults With TB Disease

NCT01424501 | Terminated Phase 2 Results

• 1 other identifier: 114886
• Study Type: interventional
• Target: 142
• Locations: 2 countries
• Sites: 6

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.

Conditions

Tuberculosis

Keywords

Tuberculosis vaccine; HIV-negative; tuberculosis treatment

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With Any and Grade 3 Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activities. Grade 3 redness/swelling = redness/swelling spreading beyond (\>) 100 millimeters (mm) of injection site.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, malaise, myalgia and temperature \[body temperature equal to or above (≥) 37.5 degrees Celsius (°C)\]. Any = occurrence of any solicited general symptom regardless of their intensity grade or relationship to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = body temperature above (\>) 39.5°C. Related = event assessed by the investigator as causally related to the study vaccination.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Adverse Events (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

  During the 30 day (Days 0-29), after vaccination

• Number of Subjects With Serious Adverse Events (SAEs)

  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  Up to day 210

Secondary Outcomes (22)

• Number of Subjects With Anti-Mycobacterium Tuberculosis Fusion Protein M72 Antibodies

  Prior to dose 1 (Day 0), post-dose 1 (Day 30), post-dose 2 (Days 60 and 210)

• Concentrations of Anti-M72 Antibodies

  Prior to dose 1 (Day 0), post-dose 1 (Day 30), post-dose 2 (Days 60 and 210)

• Frequency of M72-specific Cluster of Differentiation 4 (CD4+) T-cells Expressing Any Combination of the Different Immune Markers

  Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)

• Frequency of M72-specific CD4+ T-cells Expressing at Least 2 Immune Markers Among 6

  Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)

• Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Cytokines

  Prior to dose 1 (Day 0), post-dose 1 (Days 7 and 30), post-dose 2 (Days 37, 60 and 210)

Study Arms (6)

Group A

EXPERIMENTAL

Subjects from TB-treated cohort will receive 2 doses of GSK's investigational vaccine GSK 692342.

Biological: GSK Biologicals' investigational TB vaccine GSK 692342

Group B

PLACEBO COMPARATOR

Subjects from TB-treated cohort will receive 2 doses of physiological Saline.

Biological: Placebo

Group C

EXPERIMENTAL

Subjects from TB-treatment cohort will receive 2 doses of GSK's investigational vaccine GSK 692342.

Biological: GSK Biologicals' investigational TB vaccine GSK 692342

Group D

PLACEBO COMPARATOR

Subjects from TB-treatment cohort will receive 2 doses of physiological Saline.

Biological: Placebo

Group E

EXPERIMENTAL

Subjects from TB-naive cohort will receive 2 doses of GSK's investigational vaccine GSK 692342.

Biological: GSK Biologicals' investigational TB vaccine GSK 692342

Group F

PLACEBO COMPARATOR

Subjects from TB-naive cohort will receive 2 doses of physiological Saline.

Biological: Placebo

Interventions

GSK Biologicals' investigational TB vaccine GSK 692342 BIOLOGICAL

Intramuscular injection, 2 doses

Group A; Group C; Group E

Placebo BIOLOGICAL

Intramuscular injection, 2 doses

Group B; Group D; Group F

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Tallinn, 10117, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, 220, Taiwan

Location

GSK Investigational Site

Taipei, Taiwan

Location

GSK Investigational Site

Taoyuan Hsien, 333, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 36355775 DERIVED

• 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.

  PMID: 27553419 DERIVED

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Limitations and Caveats

Due to a safety signal found at a planned interim safety review, further conduct of this safety study is not recommended hence the study was terminated.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 29, 2011
• Study Start: November 14, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 10, 2014
• Last Updated: August 20, 2018
• Results First Posted: January 24, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

TW (4); ES (2)