| Protocol No: | ECCT/13/08/01 | Date of Protocol: | 29-03-2013 |
| Study Title: |
A phase IIb, double-blind, randomised, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of GSK Biologicals’ candidatetuberculosis (TB) vaccine GSK 692342 against TB disease, in healthy adults aged 18-50 years, living |
| A phase IIb, double-blind, randomised, placebocontrolled study to evaluate the efficacy, safety and immunogenicity of GSK Biologicals’ candidate tuberculosis (TB) vaccine GSK 692342 against TB disease, in adults aged 18-50 years, living in a TB endemic region. | |
| Study Objectives: | Primary Efficacy Objective: To evaluate the protective efficacy of two doses of the M72/AS01E candidate vaccine against definite pulmonary TB disease, meeting the first case definition, as compared to placebo. Safety objective: To assess the safety and reactogenicity of two doses of the M72/AS01E candidate vaccine Immunogenicity objective: To assess the immunogenicity of two doses of the M72/AS01E candidate vaccine. |
| Laymans Summary: | Kenya is 10th among the 22 countries with the highest burden of TB (WHO 2010) BCG is currently the only licensed TB vaccine. It reduces risk of severe forms of TB, but protection against pulmonary TB is incomplete. An effective prophylactic TB vaccine is needed. Seven thousand healthy, HIV negative adults in TB endemic regions will be randomised 1:1 to receive two identical doses M72/AS01E or placebo. Through a 36 month follow up period, initial efficacy, further safety and immunogenicity data on M72/AS01E vaccine will be accrued. The outcome of this phase IIb trial will determine whether the candidate advances to phase III licensure trials |
| Abstract of Study: |
This Phase IIb study is designed to evaluate the protective efficacy of the M72/AS01 E candidate tuberculosis vaccine This study is an international, multicentre, phase IIb, double- blind, randomized, controlled trial. There will be follow-up for efficacy for approximately 3 years after vaccination via regular visits or contacts to screen for possible TB. Subjects will also be asked to recognise signs and symptoms compatible with TB disease and to self-report for clinical evaluation. Subjects with clinical suspicion of pulmonary TB will be assessed with confirmatory diagnostic testing using a Nucleic Acid Amplification Test (Xpert MTB/RIF assay, Cepheid) and microbiological culture. Subjects diagnosed with TB will be referred for TB treatment according to local clinical practice.
A sub-cohort of subjects will be selected for specific follow- up for safety (solicited adverse events [AE] and selected Biochemistry and Complete Blood Count [CBC]) and immunogenicity. Unsolicited AEs, serious adverse events (SAEs), potential immune-mediated diseases (pIMDs), AEs leading to withdrawal and pregnancies will be recorded for all subjects. An IFN- positive T cell response induced by past or present Mtb infection, as measured by the QuantiFERON® TB Gold (QFTG) assay (Cellestis), will be evaluated at baseline for all subjects, at study end (Year 3) for all subjects QFTG-negative at baseline and yearly for subjects in the safety and immune sub-cohort. In addition, a QFTG assay will be performed whenever a subject isdiagnosed with TB disease. |
| 1 |
A phase IIb, double-blind, randomised, placebo controlled study to evaluate the efficacy, safety and immunogenicity of GSK Biologicals’ candidate tuberculosis (TB) vaccine GSK 692342 against TB disease, in adults aged 18-50 years, living in a TB endemic region. Rationale for the study and study design: The burden of Mycobacterium tuberculosis (Mtb) disease, particularly when compounded by Human Immunodeficiency virus (HIV)-infection and the emergence of multi-drug resistant (MDR) and extensively-drug resistant strains (XDR), is significant in TB endemic countries/regions. In 2010, approximately 40% of TB cases were reported in India and China, of which up to 80% were pulmonary in nature [WHO, 2011]. Africa accounted for a further 24% of cases (of which 25% were in South Africa), with most cases in young adults. Prevention of TB disease is not only preferable to treatment of the disease for public health reasons, but an effective prophylactic TB vaccine would also lead to a considerable return in health benefits. In TB endemic settings the incidence of pulmonary TB disease is higherin people who have been infected with Mtb as evidenced by a positive Interferon gamma release assay (IGRA). For the present first phase II proof-of-concept trial focussing on this IGRA+ adult population maximizes the trial efficiency by increasing the event rate in the control group. (Amended: 29 January 2014)
This Phase IIb study is designed to evaluate the protective efficacy of the M72/AS01E candidate TB vaccine against definite pulmonary TB disease not associated with HIVCONFIDENTIAL This study is an international, multicentre, phase IIb, double-blind, randomized, controlled trial. There will be follow-up for efficacy for up to 3 years after vaccination via regular visits or contacts to screen for possible TB. Subjects will also be asked to recognise signs and symptoms compatible with TB disease and to self-report for clinical evaluation. Subjects with clinical suspicion of pulmonary TB will be assessed with confirmatory diagnostic testing using a Nucleic Acid Amplification Test (Xpert MTB/RIF assay, Cepheid) and microbiological culture. Subjects diagnosed with TB will be referred for TB treatment according to local clinical practice. (Amended: 29 January 2014)
Participating sites will use standardised case definitions for efficacy endpoints and a structured approach to caseassessment as outlined in this study protocol will be used. An Independent Data Monitoring Committee (IDMC) has been constituted for this study to perform periodic safety reviews of the safety data. (Amended: 29 January 2014) |