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

NCT04608955 | Completed Phase 2 DMC

• 1 other identifier: JYB0201
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Tuberculosis

Keywords

Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Time to positive (TTP)

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

  Day 0-14.

• Early bactericidal activity (EBA) of WX-081

  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.

  Day 0-14.

Secondary Outcomes (10)

• change of electrocardiogram QT interval

  Measured through 8 Weeks.

• The percentage of participants with sputum culture-negative conversion.

  Measured through 8 Weeks.

• Rate of change of colony forming units (CFU)

  Measured through 8 Weeks.

• The percentage of participants with sputum smear-negative conversion.

  Measured through 8 Weeks.

• heart rate

  Measured through 8 Weeks.

Study Arms (6)

Arm A: WX-081

EXPERIMENTAL

Participants with newly-treated drug sensitivity tuberculosis receive WX-081 150mg orally once daily for 2 weeks.

Drug: WX-081

Arm B: WX-081

EXPERIMENTAL

Participants with newly-treated drug sensitivity tuberculosis receive WX-081 300mg orally once daily for 2 weeks.

Drug: WX-081

Arm C: WX-081

EXPERIMENTAL

Participants with newly-treated drug sensitivity tuberculosis receive WX-081 450mg orally once daily for 2 weeks.

Drug: WX-081

Arm D: Standard treatment

ACTIVE COMPARATOR

Participants with newly-treated drug sensitivity tuberculosis receive standard treatment for two weeks.

Drug: Standard treatment

Arm E: WX-081+MBT

EXPERIMENTAL

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; Drug: Multi-drug background treatment (MBT)

Arm F: Bedaquiline+MBT

ACTIVE COMPARATOR

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; Drug: Multi-drug background treatment (MBT)

Interventions

WX-081 DRUG

WX-081 is not licensed yet. WX-081 will be used in arms A, B, C, WX-081+MBT.

Arm A: WX-081; Arm B: WX-081; Arm C: WX-081; Arm E: WX-081+MBT

Bedaquiline DRUG

This licensed drug will be used in arm F as positive comparator.

Arm F: Bedaquiline+MBT

Standard treatment DRUG

Standard treatment will be used in arm D as positive comparator, according to the recommendations of WHO guidelines for diagnosis and treatment of tuberculosis.

Arm D: Standard treatment

Multi-drug background treatment (MBT) DRUG

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.

Arm E: WX-081+MBT; Arm F: Bedaquiline+MBT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged between 18 and 65 years.
• Body weight between 40 and 90 kg.
• 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.
• 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.
• Patients must consent to HIV-testing, or provide HIV-negative report within 6 months.
• Women are not breastfeeding or pregnant, and agree to practice effective contraception throughout the trial.
• 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.

You may not qualify if:

• Patients with HIV infection.
• Patients with miliary tuberculosis or extrapulmonary tuberculosis judged by the investigator.
• Patients with certain QT/QTc interval characteristics as described in the protocol.
• 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.
• Patients who have participated in other clinical studies within 8 weeks prior to trial start.
• Patients having a known or suspected hypersensitivity or serious adverse reaction to drugs used in this trial.
• Women who are pregnant, breastfeeding, or planning to become pregnant.
• 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.

Sponsors & Collaborators

• Shanghai Jiatan Pharmatech Co., Ltd: lead

Study Sites (1)

Beijing Chest Hospital affiliated to Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Related Publications (1)

• Huang Z, Luo W, Xu D, Guo F, Yang M, Zhu Y, Shen L, Chen S, Tang D, Li L, Li Y, Wang B, Franzblau SG, Ding CZ. Discovery and preclinical profile of sudapyridine (WX-081), a novel anti-tuberculosis agent. Bioorg Med Chem Lett. 2022 Sep 1;71:128824. doi: 10.1016/j.bmcl.2022.128824. Epub 2022 May 27.

  PMID: 35636648 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

sudapyridine; bedaquiline

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Song AiYun, MD

  Shang hai Jiatan Pharma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: October 10, 2020
• First Posted: October 30, 2020
• Study Start: October 16, 2020
• Primary Completion: April 13, 2022
• Study Completion: April 13, 2022
• Last Updated: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)