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

Sponsor
Shanghai Jiatan Pharmatech Co., Ltd (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04608955
Collaborator
(none)
84
1
6
26.6
3.2

Study Details

Study Description

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
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

Study Type:
Interventional
Anticipated Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Parallel AssignmentParallel 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 :
Sep 12, 2020
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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

Primary Outcome Measures

  1. Time to positive (TTP) [Day 0-14.]

    TTP is measured as time to sputum culture positivity in Liquid Culture Media.

  2. Early bactericidal activity (EBA) of WX-081 [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 [Measured through 8 Weeks.]

    QT interval is calculated as QTcF in milliseconds (ms)

  2. The percentage of participants with sputum culture-negative conversion. [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) [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. [Measured through 8 Weeks.]

    Percentage of participants with an occurrence of sputum smear-negative through 8 weeks.

  5. heart rate [Measured through 8 Weeks.]

    heart rate in times per minute.

  6. blood pressure [Measured through 8 Weeks.]

    blood pressure in mmHg

  7. Maximum plasma concentration (Cmax) [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) [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)) [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) [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

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Beijing Chest Hospital affiliated to Capital Medical University Beijing Beijing China 101149

Sponsors and Collaborators

  • Shanghai Jiatan Pharmatech Co., Ltd

Investigators

  • Study Chair: Song AiYun, MD, Shang hai Jiatan Pharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shanghai Jiatan Pharmatech Co., Ltd
ClinicalTrials.gov Identifier:
NCT04608955
Other Study ID Numbers:
  • JYB0201
First Posted:
Oct 30, 2020
Last Update Posted:
Dec 15, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 15, 2021