Back to resultsFS-1 Drug for Treatment of Multiple Drug-resistant Tuberculosis (FS-1)
Primary Purpose
Tuberculosis, MDR
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
FS-1
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis, MDR focused on measuring Tuberculosis, Multi-drug resistant TB, TB treatment
Eligibility Criteria
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
Sites / Locations
- Semey Medical University
- West Kazakhstan Marat Ospanov Medical University
- National scientific center of phthisiopulmonology Ministry of health of the Republic of Kazakhstan
- Center of Phthisiopulmonology of the Public Health Administration of Almaty
- Karaganda Medical University
- National Center of Phthisiatry
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
A
B
Arm Description
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.
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).
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
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.
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.
The median time to occurrence of negative sputum microscopy result
The average time between positive and negative sputum smear microscopy results during the treatment.
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.
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.
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.
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).
Full Information
NCT ID
NCT02607449
First Posted
November 11, 2015
Last Updated
May 17, 2022
Sponsor
Scientific Center for Anti-infectious Drugs, Kazakhstan
Collaborators
Phthisiopulmonology Center of Almaty, Kazakhstan, National Scientific Center of Phthisiopulmonology, Kazakhstan, Karaganda Medical University, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan, Semey State Medical University, National Center of Phthisiatry, Bishkek, Kyrgyzstan, Invivo laboratory, Kazakhstan
1. Study Identification
Unique Protocol Identification Number
NCT02607449
Brief Title
FS-1 Drug for Treatment of Multiple Drug-resistant Tuberculosis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
October 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scientific Center for Anti-infectious Drugs, Kazakhstan
Collaborators
Phthisiopulmonology Center of Almaty, Kazakhstan, National Scientific Center of Phthisiopulmonology, Kazakhstan, Karaganda Medical University, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan, Semey State Medical University, National Center of Phthisiatry, Bishkek, Kyrgyzstan, Invivo laboratory, Kazakhstan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, MDR
Keywords
Tuberculosis, Multi-drug resistant TB, TB treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
344 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
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.
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
FS-1
Intervention Description
FS-1 is a liquid solution for internal intake and has antimicrobial and antibacterial activities.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo without any active pharmaceutical ingredients
Primary Outcome Measure Information:
Title
Time to persistently negative sputum cultures
Description
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).
Time Frame
18 months
Title
Proportion of Patients with persistently negative sputum cultures (SCC)
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The proportion of subjects with relapse of tuberculosis
Description
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.
Time Frame
12 months
Title
Patients body weight dynamics for the period of 18 months.
Description
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.
Time Frame
18 months
Title
The median time to occurrence of negative sputum microscopy result
Description
The average time between positive and negative sputum smear microscopy results during the treatment.
Time Frame
18 months
Title
The time when TB clinical symptoms not observed
Description
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.
Time Frame
18 months
Title
Dynamics of the tuberculosis process based on subjects chest x-ray diagnosis.
Description
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.
Time Frame
18 months
Title
The incidence and severity of Adverse Events, Serious Adverse Events and drug related Adverse Drug Reactions
Description
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.
Time Frame
18 months
Title
Assessment of the study drug effect on thyroid gland function
Description
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).
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amirkan A Azembayev, Cond.Phar.Sc.
Organizational Affiliation
JSC "Scientific Center for Anti-infectious Drugs"
Official's Role
Study Director
Facility Information:
Facility Name
Semey Medical University
City
Semey
State/Province
East-Kazakhstan Region
ZIP/Postal Code
071400
Country
Kazakhstan
Facility Name
West Kazakhstan Marat Ospanov Medical University
City
Aktobe
State/Province
West Kazakhstan Region
ZIP/Postal Code
030019
Country
Kazakhstan
Facility Name
National scientific center of phthisiopulmonology Ministry of health of the Republic of Kazakhstan
City
Almaty
ZIP/Postal Code
050010
Country
Kazakhstan
Facility Name
Center of Phthisiopulmonology of the Public Health Administration of Almaty
City
Almaty
ZIP/Postal Code
050030
Country
Kazakhstan
Facility Name
Karaganda Medical University
City
Karaganda
Country
Kazakhstan
Facility Name
National Center of Phthisiatry
City
Bishkek
ZIP/Postal Code
030019
Country
Kyrgyzstan
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
http://scaid.kz
Description
General information about Sponsor of the study.
URL
https://elibrary.ru/item.asp?id=24795068
Description
New approach to treatment MDR-TB
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420568/
Description
Genomic Insight into Mechanisms of Reversion of Antibiotic Resistance in Multi-Drug Resistant Mycobacterium Tuberculosis Induced by FS-1
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645197/
Description
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
URL
https://pdfs.semanticscholar.org/aa99/f23a56e4984ce275274125c48c23ee3cba10.pdf?_ga=2.196299177.40052518.1562695622-2113992793.1562695622
Description
Constraints of Drug Resistance - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics
URL
http://sbook.ru/vrasp/contents/va15711sd.pdf
Description
The effect of the Kazakhstan drug FS-1 on the outcome of multidrug-resistant pulmonary tuberculosis in complex anti-tuberculosis therapy
URL
http://sibac.info/conf/med/xliv/42595
Description
Anti-tuberculosis activity of new drug FS-1
Learn more about this trial
FS-1 Drug for Treatment of Multiple Drug-resistant Tuberculosis
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