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Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With WX-081 (WX-081)

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ClinicalTrials.gov Identifier: NCT04608955
Recruitment Status : Recruiting
First Posted : October 30, 2020
Last Update Posted : December 15, 2021
Sponsor:
Information provided by (Responsible Party):
Shanghai Jiatan Pharmatech Co., Ltd

Study Description
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Brief Summary:
This is a multi-center, randomized, parallel, open-label, positive-controlled Phase 2 clinical trial, which aims to evaluate the early bactericidal activity, safety and tolerability of WX-081 in patients with drug-naive&susceptible and drug-resistant tuberculosis. Also the efficacy of WX-081 will be explored in participants with drug-resistant tuberculosis.

Condition or disease Intervention/treatment Phase
Pulmonary Tuberculosis Drug: WX-081 Drug: Bedaquiline Drug: Standard treatment Drug: Multi-drug background treatment (MBT) Phase 2

Detailed Description:

This is a Phase 2, multi-center, randomized, parallel, open-label, positive-controlled clinical trial. The objective of this trial is to evaluate the early bactericidal activity, safety and tolerability of WX-081 patients with drug-naive&susceptible and drug-resistant tuberculosis. and the efficacy in participants with drug-resistant tuberculosis.

This trial will be divided into core research stage (stage 1) and extended research stage (stage 2). During stage 1, a panel of 44 participants with drug-naive&susceptible tuberculosis will be randomized to receive either WX-081(including 3 groups:150mg qd, 300mg qd, 450mg qd. n=12 per group) or standard treatment (n=8) for 2 weeks, and then followed by a follow-up period of 2 weeks. A panel of 40 participants with drug-resistant tuberculosis will be randomized to receive either WX-081 (400mg qd, n=20) or bedaquiline (400mg qd, n=20) for 2 weeks. During stage 2, the 40 participants with drug-resistant tuberculosis will receive WX-081(150mg qd) + MBT treatment (ie. multi-drug background treatment) and bedaquiline (200mg tiw) +MBT treatment for 6 weeks respectively, and then followed by a follow-up period of 4 weeks.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Positive-controlled Phase 2 Clinical Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of WX-081 in Participants With Drug-naive&Susceptible or Drug-Resistant Pulmonary Tuberculosis
Actual Study Start Date : September 12, 2020
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: WX-081
Participants with newly-treated drug sensitivity tuberculosis receive WX-081 150mg orally once daily for 2 weeks.
 Drug: WX-081
WX-081 is not licensed yet. WX-081 will be used in arms A, B, C, WX-081+MBT.
Experimental: Arm B: WX-081
Participants with newly-treated drug sensitivity tuberculosis receive WX-081 300mg orally once daily for 2 weeks.
 Drug: WX-081
WX-081 is not licensed yet. WX-081 will be used in arms A, B, C, WX-081+MBT.
Experimental: Arm C: WX-081
Participants with newly-treated drug sensitivity tuberculosis receive WX-081 450mg orally once daily for 2 weeks.
 Drug: WX-081
WX-081 is not licensed yet. WX-081 will be used in arms A, B, C, WX-081+MBT.
Active Comparator: Arm D: Standard treatment
Participants with newly-treated drug sensitivity tuberculosis receive standard treatment for two weeks.
 Drug: Standard treatment
Standard treatment will be used in arm D as positive comparator, according to the recommendations of WHO guidelines for diagnosis and treatment of tuberculosis.
Experimental: Arm E: WX-081+MBT
Participants with drug-resistant tuberculosis receive WX-081 400mg orally once daily for 2 weeks, and then MBT+ WX-081 150mg orally once daily for 6 weeks.
 Drug: WX-081
WX-081 is not licensed yet. WX-081 will be used in arms A, B, C, WX-081+MBT.

Drug: Multi-drug background treatment (MBT)
MBT will be used in arm E, F as background treatment. The drugs used in MBT are all licensed drugs, and the treatment complies with the recommendations of WHO guidelines for diagnosis and treatment of tuberculosis.
Active Comparator: Arm F: Bedaquiline+MBT
Participants with drug-resistant tuberculosis receive Bedaquiline 400mg orally once daily for 2 weeks, and then MBT+ Bedaquiline 200mg orally 3 times per week for 6 weeks.
 Drug: Bedaquiline
This licensed drug will be used in arm F as positive comparator.

Drug: Multi-drug background treatment (MBT)
MBT will be used in arm E, F as background treatment. The drugs used in MBT are all licensed drugs, and the treatment complies with the recommendations of WHO guidelines for diagnosis and treatment of tuberculosis.


Outcome Measures
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Primary Outcome Measures :
  1. Time to positive (TTP) [ Time Frame: Day 0-14. ]
    TTP is measured as time to sputum culture positivity in Liquid Culture Media.

  2. Early bactericidal activity (EBA) of WX-081 [ Time Frame: Day 0-14. ]
    EBA is measured as the mean rate of colony forming unit (log10CFU) of mycobacterium tuberculosis per ml sputum on solid medium in different time periods.


Secondary Outcome Measures :
  1. change of electrocardiogram QT interval [ Time Frame: Measured through 8 Weeks. ]
    QT interval is calculated as QTcF in milliseconds (ms)

  2. The percentage of participants with sputum culture-negative conversion. [ Time Frame: Measured through 8 Weeks. ]
    Percentage of participants with an occurrence of sputum culture-negative through 8 weeks.

  3. Rate of change of colony forming units (CFU) [ Time Frame: Measured through 8 Weeks. ]
    Rate of change of colony forming units (CFU) of mycobacterium tuberculosis on sputum culture through 8 weeks.

  4. The percentage of participants with sputum smear-negative conversion. [ Time Frame: Measured through 8 Weeks. ]
    Percentage of participants with an occurrence of sputum smear-negative through 8 weeks.

  5. heart rate [ Time Frame: Measured through 8 Weeks. ]
    heart rate in times per minute.

  6. blood pressure [ Time Frame: Measured through 8 Weeks. ]
    blood pressure in mmHg

  7. Maximum plasma concentration (Cmax) [ Time Frame: At day1 and 14. ]
    Blood samples will be taken at different time points before and after administration on Day1 and Day14 of treatment.

  8. Time to reach maximum plasma concentration (Tmax) [ Time Frame: At day1 and 14. ]
    Blood samples will be taken at different time points before and after administration on Day1 and Day14 of treatment.

  9. Area under the plasma concentration versus time curve (AUC(0-t)) [ Time Frame: At day1 and 14. ]
    Blood samples will be taken at different time points before and after administration on Day1 and Day14 of treatment.

  10. Terminal plasma half-life (t1/2) [ Time Frame: At day1 and 14. ]
    Blood samples will be taken at different time points before and after administration on Day1 and Day14 of treatment.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged between 18 and 65 years.
  2. Body weight between 40 and 90 kg.
  3. Newly-treated drug sensitivity tuberculosis: clinically diagnosed as pulmonary tuberculosis, without treatment, sputum smear-positive for acid-fast bacilli (AFB at least 1+), and no resistant to rifampicin or isoniazid in the drug sensitivity test.
  4. Drug-resistant tuberculosis: re-treatment pulmonary tuberculosis patients, diagnosed as rifampicin resistance (RR-TB) or isoniazid and rifampicin resistance (MDR-TB) by molecular biology methods, and sputum smear-positive for acid-fast bacilli. Patients must be willing to discontinue all TB drugs to allow 7 days washout.
  5. Patients must consent to HIV-testing, or provide HIV-negative report within 6 months.
  6. Women are not breastfeeding or pregnant, and agree to practice effective contraception throughout the trial.
  7. Provide voluntary and written informed consent prior to all trial-related procedures, agree to comply with the requirements and restrictions listed in the informed consent form and agreement.

Exclusion Criteria:

  1. Patients with HIV infection.
  2. Patients with miliary tuberculosis or extrapulmonary tuberculosis judged by the investigator.
  3. Patients with certain QT/QTc interval characteristics as described in the protocol.
  4. the patients have a history of, or current evidence of clinically relevant unstable or severe cardiovascular, kidney, liver, blood, tumor, endocrine and metabolic, mental or rheumatic diseases, or any other condition that will not be suitable to participate in this study, according to the judgement of the investigator.
  5. Patients who have participated in other clinical studies within 8 weeks prior to trial start.
  6. Patients having a known or suspected hypersensitivity or serious adverse reaction to drugs used in this trial.
  7. Women who are pregnant, breastfeeding, or planning to become pregnant.
  8. Current or past history of alcohol and/or drug use that, in the investigator's opinion, would compromise the participant's safety or compliance to the study protocol procedures.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04608955


Contacts
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Contact: Juncai Xu, Master 00862161553050 jcxu@joyopharma.com
Contact: Lei Li, Master 00862161553050 lilei@joyopharma.com

Locations
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China, Beijing
Beijing Chest Hospital affiliated to Capital Medical University Recruiting
Beijing, Beijing, China, 101149
Contact: Zhao WeiJie, Master    08601089509157    zhaoweijie415@163.com   
Principal Investigator: Chu NaiHui, MD         
Sponsors and Collaborators
Shanghai Jiatan Pharmatech Co., Ltd
Investigators
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Study Chair: Song AiYun, MD Shang hai Jiatan Pharma
More Information
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Responsible Party: Shanghai Jiatan Pharmatech Co., Ltd
ClinicalTrials.gov Identifier: NCT04608955    
Other Study ID Numbers: JYB0201
First Posted: October 30, 2020    Key Record Dates
Last Update Posted: December 15, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Shanghai Jiatan Pharmatech Co., Ltd:
Tuberculosis
Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
 Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Bedaquiline
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents