FS-1 Drug for Treatment of Multiple Drug-resistant Tuberculosis

Study Overview
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Brief Summary
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Drug-resistant tuberculosis is becoming a major problem for the whole humanity, and development of new Anti-TB drugs is of great importance. Since Kazakhstan is a country with the high burden of tuberculosis, the Government of the Republic of Kazakhstan has founded initiative on the development of new Anti-TB drug to treat drug-resistant forms of this infectious disease. JSC Scientific Center for Anti-infectious Drugs has developed original drug FS-1 for the treatment of multidrug resistant tuberculosis (MDR-TB).

Detailed Description
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Phase 3 clinical study of FS-1 drug is a randomized, interventional, multicenter, placebo-controlled (add-on), double-blind and two arms trial. The study consists of two following phases: treatment phase - 6 months and follow-up phase 12 months. It is planned to recruit 480 patients with verified MDR-TB diagnosis. All data will be compiled in an Electronic Data Capture System with further statistical analysis according to approved Statistical Analytical Plan.

Official Title
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Randomized, Placebo-controlled Study of Safety and Therapeutic Efficacy of the Drug FS-1 in the Oral Dosage Form in Drug-resistant Pulmonary Tuberculosis

Conditions
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Tuberculosis, MDR

Intervention / Treatment
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* Drug: FS-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects suffering from a multidrug-resistant form of pulmonary tuberculosis which is defined by: MDR Tuberculosis confirmed by microbiology test at screening. resistance to isoniazid and rifampicin demonstrated by drug susceptibility test susceptiblity of TB bacteria to fluoroquinolones and aminoglycoside/capreomycin all ethnicities, intellectually capable of understanding their own condition and the requirements of the study protocol Willing to freely and voluntarily give signed informed consent Willing and capable to comply with all requirements of the protocol Exclusion Criteria: Pregnancy and breast-feeding; Patients with decompensated concomitant diseases (cardiovascular, renal, hepatic failure) that may affect the conduct of the study; Severe mental disorders; Allergy to iodine-containing drugs, hypersensitivity to iodine; Intolerance to second-line drugs; Epidermomycosis Socially maladjusted patients suffering from alcoholism and drug addiction; Hypothyroidism; Hashimoto's thyroiditis; TB treatment for more than two months before the start of the study; Not willing to adhere to TB therapy; Exclusion Criteria during the study: at the discretion of the researcher, if the continuation of the study is harmful to the patient; side effects related with the study drug patient's decision to stop participation in study appearance of any exclusion criteria during study

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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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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Standard TB treatment+ treatment regiment with FS-1 drug. Study drug was given to the patients orally once per day in dose of 2.5 mg/kg along with other prescribed TB drugs. | Drug: FS-1<br>* FS-1 is a liquid solution for internal intake and has antimicrobial and antibacterial activities.<br>|
| Placebo Comparator: B<br>Standard TB treatment + treatment regiment with a placebo. Instead of study drug the placebo was given to the patients orally once per day along with other prescribed TB drugs (in quntity equal to study drug). | Drug: Placebo<br>* Placebo without any active pharmaceutical ingredients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to persistently negative sputum cultures | Time from the start of treatment with study drug to the first negative M. tuberculosis sputum culture on solid medium followed by 4 consecutive negative results with an interval of at least 30 days. Measured in months. Estimated population: randomized subjects who took at least 70% of planned study drug doses; having a positive bacterial culture M. tuberculosis at the baseline; who missed less than 2 consecutive visits or less than 14 consecutive days of study drug treatment (modified ITT analysis). | 18 months | 
| Proportion of Patients with persistently negative sputum cultures (SCC) | Sputum culture conversion (SCC) is a persistently negative result of the sputum culture at one year from the patients who had sputum samples positive for growth of M. tuberculosis at baseline and not followed by any positive culture until the end of the trial. SCC corresponds to the outcome cured if at least 5 negative bacteriological cultures is recorded (on solid medium) during 12 months with an interval of at least 30 days. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with relapse of tuberculosis | Relapse is defined when patient received full study drug treatment course (6 months) and bacteriological culture become again positive after 5 negative bacteriological cultures (on solid medium) during 12 months with an interval of at least 30 days. | 12 months | 
| Patients body weight dynamics for the period of 18 months. | Comparison of subjects' weight, using as the baseline subjects' weight before the start of the treatment with the subjects' weight during the treatment cycle with the study drug (6 months) and during 12 months of follow-up period. | 18 months | 
| The median time to occurrence of negative sputum microscopy result | The average time between positive and negative sputum smear microscopy results during the treatment. | 18 months | 
| The time when TB clinical symptoms not observed | Assessment of period between TB clinical symptoms and their disappearance. Observed of TB clinical symptoms are as follows: chest pain, difficulties to breath, cough, sputum, intoxication symptoms. | 18 months | 
| Dynamics of the tuberculosis process based on subjects chest x-ray diagnosis. | The positive dynamics of the subject X-ray picture of the tuberculous process is characterized by the closure of TB caused cavities, a decrease of lung infiltration, nodular lesions, pleural effusion and lymphadenopathy. | 18 months | 
| The incidence and severity of Adverse Events, Serious Adverse Events and drug related Adverse Drug Reactions | Assessment of Adverse Events and Drug Reactions during the study (6 months of treatment and 12 months of follow-up period). Adverse event (AE) is any untoward medical occurrence in subject administered the study drug and that does not necessarily have a causal relationship with this treatment. AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to the study drug. Serious Adverse Event is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. Adverse drug reaction - all noxious and unintended responses to the study drug, when a causal relationship between the study drug and an adverse event is at least a reasonable possibility. | 18 months | 
| Assessment of the study drug effect on thyroid gland function | Assessment of thyroid hormones and antibodies in the blood (free triiodothyronine (FT3), free thyroxine (FT4), total thyroxine (TT4),total triiodothyronine (TT3),thyroid stimulating hormone (TSH), antibodies to thyroglobulin and thyroid peroxidase), and results of ultrasound of the thyroid gland before treatment, during treatment (6 months) and during the follow-up period (12 months). | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Multi-drug resistant TB, TB treatment