Study to Check the Efficacy and Safety of Recombinant BCG Vaccine in Prevention of TB Recurrence

Study Overview
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Brief Summary
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This is a Phase II/III trial with two groups of adults successfully cured of category 1 pulmonary TB receiving either VPM1002 or placebo. Single dose of VPM1002 / placebo will be administered to calculate efficacy of the vaccine against TB recurrence.

Detailed Description
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The study is designed as a multicenter, double-blinded, randomized, placebo-controlled trial with two groups of category 1 pulmonary TB patients who have successfully completed ATT and declared cured by bacteriological confirmation. The eligible participants will be randomized in 1:1 ratio to receive single dose of either VPM1002 or placebo. After study vaccination, participants will be followed up for one year. Any suspected TB case during follow up will be further evaluated and bacteriologically confirmed. Study participants will be actively followed up for 2 months post-vaccination for any solicited local and regional reaction. SAEs will be recorded and reported throughout study participation.

Official Title
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A Multicenter Phase II/III Double-Blind, Randomized, Placebo Controlled Study To Evaluate The Efficacy And Safety Of VPM1002 In The Prevention Of Tuberculosis (TB) Recurrence In Pulmonary TB Patients After Successful TB Treatment

Conditions
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Prevention of TB Recurrence

Intervention / Treatment
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* Biological: VPM1002 (Recombinant BCG Vaccine)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥18 and ≤65 years. Bacteriologically confirmed Category I pulmonary TB patients (including controlled diabetics with HbA1c level ≤7% and non-diabetics) who successfully completed ATT as per national guidelines. Must have a sputum sample showing bacteriologic confirmation of cure - defined as smear negative. Female participants who are currently using reliable methods of birth control, have a negative pregnancy test during screening and have no intention to become pregnant for at least 3 months post-vaccination. Participant must intend to remain in the area during the study period. Exclusion Criteria: Reactive serology for HIV History of extrapulmonary TB Known or suspected impairment of immunological function Pregnant and / or lactating female participants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VPM1002 (Recombinant BCG vaccine)<br> | Biological: VPM1002 (Recombinant BCG Vaccine)<br>* VPM1002 is a formulated, lyophilized cake of live recombinant Mycobacterium bovis rBCGÄureC::Hly+; VPM1002. VPM1002 is the active pharmaceutical ingredient. It is a genetically modified BCG vaccine derived from the Mycobacterium bovis BCG subtype Prague characterized as rBCGÄureC::Hly+. Single dose of VPM1002 is administered intradermally.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Single dose of Placebo is administered intradermally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of bacteriologically confirmed TB recurrence cases | Percentage of TB recurrence patients who have previously been successfully treated for TB, were declared cure and are now diagnosed with a new episode of bacteriologically confirmed recurrent TB after at least 2 months from vaccination. | 2-12 months post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of overall TB recurrence (i.e. either bacteriologically confirmed or clinically diagnosed TB recurrence) | Percentage of TB recurrence patients who have previously been successfully treated by for TB, were declared cure and are now diagnosed with a new episode of either bacteriologically confirmed or clinically diagnosed recurrent TB after at least 2 months from vaccination. | 2-12 months post-vaccination | 
| Safety assessed by Solicited local and regional reactogenicity and Unsolicited adverse events and SAEs | Solicited local and regional reactogenicity events within 2 months following study vaccination Unsolicited adverse events and SAEs throughout the study period | Throughout study participation i.e.12 months post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant BCG vaccine, Category 1 pulmonary tuberculosis, Recurrence, Efficacy