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

Tuberculosis, MDR Clinical Trial

— FS-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607449
• Other study ID #: TP-004 V 5.1
• Status: Completed
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: October 2020

Study information

• Verified date: May 2022
• Source: Scientific Center for Anti-infectious Drugs, Kazakhstan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: October 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, MDR
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• FS-1
FS-1 is a liquid solution for internal intake and has antimicrobial and antibacterial activities.
• Placebo
Placebo without any active pharmaceutical ingredients

Locations

Country	Name	City	State
Kazakhstan	West Kazakhstan Marat Ospanov Medical University	Aktobe	West Kazakhstan Region
Kazakhstan	Center of Phthisiopulmonology of the Public Health Administration of Almaty	Almaty
Kazakhstan	National scientific center of phthisiopulmonology Ministry of health of the Republic of Kazakhstan	Almaty
Kazakhstan	Karaganda Medical University	Karaganda
Kazakhstan	Semey Medical University	Semey	East-Kazakhstan Region
Kyrgyzstan	National Center of Phthisiatry	Bishkek

Sponsors (8)

Lead Sponsor	Collaborator
Scientific Center for Anti-infectious Drugs, Kazakhstan	Invivo laboratory, Kazakhstan, Karaganda Medical University, National Center of Phthisiatry, Bishkek, Kyrgyzstan, National Scientific Center of Phthisiopulmonology, Kazakhstan, Phthisiopulmonology Center of Almaty, Kazakhstan, Semey State Medical University, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan

Countries where clinical trial is conducted

Kazakhstan,  Kyrgyzstan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Anti-tuberculosis activity of new drug FS-1
•   Complete genome sequence of the multi-drug resistant clinical isolate Mycobacterium tuberculosis 187.0 used to study an effect of drug susceptibility reversion by drug FS-1
•   Constraints of Drug Resistance - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics
•   General information about Sponsor of the study.
•   Genomic Insight into Mechanisms of Reversion of Antibiotic Resistance in Multi-Drug Resistant Mycobacterium Tuberculosis Induced by FS-1
•   New approach to treatment MDR-TB
•   The effect of the Kazakhstan drug FS-1 on the outcome of multidrug-resistant pulmonary tuberculosis in complex anti-tuberculosis therapy