Efficacy and Safety Study of Immunomodulator as an Adjunct Therapy in Pulmonary Tuberculosis (TB) Retreatment Patients

Study Overview
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Brief Summary
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The purpose of the study is to study the efficacy and safety of Mycobacterium in treating patients with lung tuberculosis . Mycobacterium is a strain of bacterium which is used as a vaccine and an adjuvant drug against leprosy. This agent has also been found to be effective in the treatment of lung tuberculosis in a limited number of patients. The researchers are conducting this study in the World Health Organization (WHO) category-II of lung tuberculosis patients to see the efficacy and also to see any change in immunological parameters.

Detailed Description
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Mycobacterium w is a recently introduced immunomodulator, which has been found to be useful in rapid killing of Mycobacterium leprae. It improves the clearance of Mycobacterium leprae from the body and is thereby useful in reducing the duration of therapy significantly for multibacillary leprosy. Mycobacterium w shares an antigen with both Mycobacterium leprae as well as Mycobacterium tuberculosis. Mycobacterium w is also found to be useful in the prevention of tuberculosis in experimental animals. Previous studies on the efficacy of Mycobacterium w as an immunomodulator in pulmonary tuberculosis patients have shown higher sputum conversion rates in patients given Mycobacterium w as an adjuvant therapy along with standard anti-tuberculosis treatment. It has faster and remarkable sputum converting capacity. Similar studies conducted in pulmonary TB category -II [re-treatment as per Revised National Tuberculosis Control Programme (RNTCP), Govt. of India] patients have shown improved cure rates. Mycobacterium w is commercially available under the brand name of Immuvac injection in 0.5 ml multi dose vials approved for use as immunomodulator against Mycobacterium leprae in patients with leprosy. Each vial has 0.5 x 10^9 heat-killed bacilli in a buffered solution. It is manufactured by Cadila Pharmaceuticals Ltd.; Ahmedabad, Gujarat-382 210, India. In this clinical trial one dose consists of 0.1 ml given as an intradermal injection, which contains 10^9 bacilli. A total of 6 doses are given during the Intensive Phase (as per RNTCP, Govt. of India) of treatment. Two injections on both upper arms on day-0 and subsequently one injection on days 14, 28, 42 and 56. No injections are given during the Continuation Phase (as per RNTCP, Govt. of India) of treatment. As of now, it is not commercially available for use in TB patients as an immunomodulator. Therefore, the investigators are investigating Mycobacterium w (Mw) for its efficacy in TB patients in a double-blind placebo-controlled randomized clinical control trial fashion. We are conducting this trial in Category-II pulmonary TB patients (as per RNTCP, Govt. of India), and are assessing the outcome in the form of clinical improvement, sputum conversion and immunological parameters. This is a multi-centric trial sponsored by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India and Cadila Pharmaceuticals Ltd., India.

Official Title
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Efficacy and Safety Study of Immunomodulator (Mycobacterium w) as an Adjunct Therapy in Category-II Pulmonary Tuberculosis Along With Assessment of Immunological Parameters

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: Intra-dermal administration of Mycobacterium w


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are sputum positive for pulmonary tuberculosis and who have been treated previously for more than 1 month as per the RNTCP/WHO guidelines. Category II inclusion will mean all those patients who are Treatment after Default/Treatment Failure/Treatment Relapse. Patients who are willing to give written informed consent. Exclusion Criteria: Patients who are known to be hypersensitive to those ATTs being administered. Patients co-infected with HIV, hepatitis B or hepatitis C. Pregnant and lactating females or females of child bearing age with a urine HCG positive result 24-48 hours prior to every injection of Mw till 8 weeks. Patients with abnormal renal function, liver function or hematological tests. Seriously ill and moribund patients with complications such as low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive heart failure. Severely malnourished patients with body mass index (BMI) < 15 Severe hypoalbuminemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category II ATT according to RNTCP guidelines | Biological: Intra-dermal administration of Mycobacterium w<br>* Mw Vaccine is given as oral suspension. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks<br>* Other names: Immuvac;|
| Placebo Comparator: 2<br>In this Arm patient will receive Placebo along with Category II ATT drugs according to RNTCP guidelines | Biological: Intra-dermal administration of Mycobacterium w<br>* Mw Vaccine is given as oral suspension. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks<br>* Other names: Immuvac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time of sputum conversion as well as the early sputum conversion between the 2 groups will be evaluated. |  | from baseline (visit 2) | 
| The cure rate will be evaluated as the primary parameter of efficacy. |  | 8-9 months | 
| The relapse in patients of category II tuberculosis will be compared in both the groups. |  | at an interval of 6, 12, 18 and 24 months after the completion of the therapy | 
| Recording of any clinical adverse reactions at anytime during the study for assessment of safety |  | 2-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| An additional secondary efficacy endpoint is the patient's and physician's global assessment of the clinical cure. |  | 8-9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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India, Pulmonary Tuberculosis, Category-II tuberculosis, Immunomodulator, Mycobacterium w, Revised National Tuberculosis Control Programme, Category-II Pulmonary Tuberculosis