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

NCT01755598 | Completed Phase 2 Results

• 1 other identifier: 115616
• Study Type: interventional
• Target: 3,575
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Tuberculosis; Tuberculosis Vaccines

Keywords

Positive Interferon-γ release assay; Efficacy; Adults; Tuberculosis vaccine; Endemic region

Outcome Measures

Primary Outcomes (1)

• Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1

  The incidence rate of definite pulmonary TB disease (or 100 Person-years rate) was calculated as the number of subjects reporting at least one case (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 100. Case definition 1 = subject with clinical suspicion of pulmonary TB disease\*, with Mycobacterium tuberculosis (Mtb) complex identified from sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF (Nucleic Acid Amplification Test to detect Mtb complex and resistance to rifampicin in sputum samples) and/or microbiological culture and confirmed Human Immunodeficiency Virus (HIV)-negative at the time of TB diagnosis. \*Clinical suspicion of pulmonary TB defined as subject presenting with 1 or more of the following symptoms: unexplained cough \> 2 weeks, unexplained fever \> 1 week, night sweats, unintentional weight loss, pleuritic chest pains, haemoptysis, fatigue or shortness of breath on exertion.

  From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first

Secondary Outcomes (14)

• Incident Rates of Definite Xpert MTB/Rif Positive Pulmonary TB Disease, Not Associated With HIV-infection, Meeting the Case Definition 2

  From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first

• Incident Rates of Definite Pulmonary TB Disease, Not Associated With HIV-infection Meeting the Case Definition 3

  From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first

• Incident Rates of Microbiological Pulmonary TB Disease, Meeting the Case Definition 4

  From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first

• Incidence Rates of Clinical TB Disease, Meeting the Case Definition 5

  From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first

• Number of Subjects With Serious Adverse Events (SAEs).

  From Day 0 up to Year 3 (during the entire study period)

Study Arms (2)

M72AS01 Group

EXPERIMENTAL

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.

Biological: GSK Biologicals' investigational TB vaccine (GSK692342)

Control group

PLACEBO COMPARATOR

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.

Biological: Placebo

Interventions

GSK Biologicals' investigational TB vaccine (GSK692342) BIOLOGICAL

2 doses administered intramuscularly in the deltoid region of the arm.

M72AS01 Group

Placebo BIOLOGICAL

2 doses administered intramuscularly in the deltoid region of the arm.

Control group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Aeras: collaborator

Study Sites (9)

GSK Investigational Site

Kisumu, Kenya

Location

GSK Investigational Site

Pretoria, Gauteng, 0152, South Africa

Location

GSK Investigational Site

Soweto, Gauteng, 2013, South Africa

Location

GSK Investigational Site

Klerksdorp, North West, 2571, South Africa

Location

GSK Investigational Site

Western Cape, Western Province, South Africa

Location

GSK Investigational Site

Worcester, Western Province, 6850, South Africa

Location

GSK Investigational Site

Cape Town, 7530, South Africa

Location

GSK Investigational Site

Cape Town, 7925, South Africa

Location

GSK Investigational Site

Lusaka, Zambia

Location

Related Publications (2)

• Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, Bollaerts A, Demoitie MA, Diacon A, Evans TG, Gillard P, Hellstrom E, Innes JC, Lempicki M, Malahleha M, Martinson N, Mesia Vela D, Muyoyeta M, Nduba V, Pascal TG, Tameris M, Thienemann F, Wilkinson RJ, Roman F. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. N Engl J Med. 2019 Dec 19;381(25):2429-2439. doi: 10.1056/NEJMoa1909953. Epub 2019 Oct 29.

  PMID: 31661198 DERIVED

• Van Der Meeren O, Hatherill M, Nduba V, Wilkinson RJ, Muyoyeta M, Van Brakel E, Ayles HM, Henostroza G, Thienemann F, Scriba TJ, Diacon A, Blatner GL, Demoitie MA, Tameris M, Malahleha M, Innes JC, Hellstrom E, Martinson N, Singh T, Akite EJ, Khatoon Azam A, Bollaerts A, Ginsberg AM, Evans TG, Gillard P, Tait DR. Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis. N Engl J Med. 2018 Oct 25;379(17):1621-1634. doi: 10.1056/NEJMoa1803484. Epub 2018 Sep 25.

  PMID: 30280651 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 24, 2012
• Study Start: August 19, 2014
• Primary Completion: November 16, 2018
• Study Completion: November 16, 2018
• Last Updated: December 3, 2019
• Results First Posted: December 3, 2019

Record last verified: 2019-11

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

ZA (7); KE (1)