A Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China (PROSPECT)

A Pragmatic Randomized Controlled Trial to Evaluate the Efficacy and Safety of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Patients With Multidrug-resistant Tuberculosis in China

The purpose of this study is to evaluate efficacy and safety of an oral bedaquiline-containing multidrug-resistant tuberculosis (MDR-TB) short-course regimen (SCR) compared to an oral SCR not including bedaquiline at the end of treatment in participants with pulmonary MDR-TB in China.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis, Multidrug-Resistant
• Intervention / Treatment: Drug: Bedaquiline; Drug: Levofloxacin; Drug: Linezolid; Drug: Cycloserine; Drug: Clofazimine; Drug: Pyrazinamide; Drug: Protionamide

• Study Type: Interventional
• Enrollment (Anticipated): 212
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jingtao Gao, PhD; Phone Number: +8610-89509131; Email: jingtaogao@outlook.com

Study Locations

• China
  • Beijing, China, 101149
    • Recruiting
    • Beijing Chest Hospital
    • Contact: Mengqiu Gao
  • Beijing, China
    • Recruiting
    • The Eighth Medical Center of PLA General Hospital
    • Contact: Huiru An
  • Changsha, China
    • Recruiting
    • Changsha Central Hospital
    • Contact: Yi Pei
  • Chengdu, China
    • Recruiting
    • Public health clinical medical center of Chengdu
    • Contact: Guihui Wu
  • Chongqing, China
    • Recruiting
    • Chongqing Public Health Medical Center
    • Contact: Xiaofeng Yan
  • Fuzhou, China
    • Recruiting
    • The Pulmonary Hospital of Fuzhou in Fujian Province（The tuberculosis control and prevention Hospital of Fuzhou in Fujian Province）
    • Contact: Xiaohong Chen
  • Guiyang, China
    • Recruiting
    • Guiyang Public Health Clinical Center
    • Contact: Zhongfeng Huang
  • Hefei, China
    • Recruiting
    • Anhui Chest Hospital
    • Contact: Hua Wang
  • Heilongjiang, China
    • Recruiting
    • Infectious Disease Hospital Of Heilongjiang Province
    • Contact: Long Jin
  • Jiamusi, China
    • Not yet recruiting
    • Jiamusi Tumor Hospital
    • Contact: Xiujie Li
  • Jiangxi, China
    • Not yet recruiting
    • Jiangxi Chest Hospital
  • Shandong, China
    • Recruiting
    • Shandong Public Health Clinical Center
    • Contact: Yu Xiong
  • Shanghai, China
    • Recruiting
    • Shanghai Pulmonary Hospital
    • Contact: Wei Sha
  • Shenyang, China
    • Recruiting
    • Shenyang Chest Hospital
    • Contact: Lian Shi
  • Wuhan, China
    • Recruiting
    • Wuhan Pulmonary Hospital
    • Contact: Juan Du
  • Xi'an, China
    • Recruiting
    • Xi'an Chest Hospital
    • Contact: Fei Ren
  • Xinxiang, China
    • Recruiting
    • The First Affiliated Hospital of Xinxiang Medical University
    • Contact: Junwei Cui

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening
• Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation
• Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB)
• Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase
• Is willing to undergo human immunodeficiency virus (HIV) testing

Exclusion Criteria:

• Has received prior treatment with bedaquiline
• Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks
• Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert
• Has a known allergy or intolerance to bedaquiline or other drugs in the regimen
• Is infected with a strain of nontuberculous mycobacteria
• Is HIV-positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bedaquiline-containing Short-course Regimen (SCR); Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.	Drug: Bedaquiline; Bedaquiline uncoated tablets will be administered orally.; Other Names: SIRTURO; Drug: Levofloxacin; Levofloxacin filmcoated will be administered orally; Drug: Linezolid; Linezolid tablets will be administered orally; Drug: Cycloserine; Cycloserine capsules will be administered orally.; Drug: Clofazimine; Clofazimine capsules will be administered orally.
Experimental: Non-bedaquiline-containing Short-course Regimen (SCR); Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.	Drug: Levofloxacin; Levofloxacin filmcoated will be administered orally; Drug: Linezolid; Linezolid tablets will be administered orally; Drug: Cycloserine; Cycloserine capsules will be administered orally.; Drug: Clofazimine; Clofazimine capsules will be administered orally.; Drug: Pyrazinamide; Pyrazinamide tablets will be administered orally.; Drug: Protionamide; Protionamide enteric-coated tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment	Percentage of participants with a favorable treatment outcome at the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.	At the end of treatment (Week 40)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with a Favorable Treatment Outcome at 48 Weeks Post the End of Treatment	Percentage of participants with a favorable treatment outcome at 48 weeks post the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.	At 48 weeks post the end of treatment (Week 88)
Percentage of Participants Achieving Treatment Success at the end of Treatment	Percentage of participants achieving treatment success at the end of treatment will be reported. Treatment success is achieved if participants completed their prescribed tuberculosis (TB) treatment; or if their last 3 culture results are negative by the end of treatment, these 3 cultures must be taken on separate visits and should be after the initial 6-month treatment period.	At the end of treatment (Week 40)
Percentage of Participants with a Modified Favorable Treatment Outcome at the end of Treatment and at 48 Weeks Post end of Treatment	Percentage of participants with a modified favorable treatment outcome at the end of treatment and at 48 weeks post end of treatment will be reported. A participant's treatment outcome will be classified as modified favorable if their last 2 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 2 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.	At the end of treatment (Week 40) and at 48 weeks post end of treatment (Week 88)
Percentage of Participants Experiencing All-cause Mortality	Percentage of participants experiencing all-cause mortality will be reported.	Up to Week 88
Percentage of Participants Experiencing Grade 3 or Greater Treatment-emergent Adverse Events (TEAEs) During Study Treatment and Follow-up	Percentage of participants experiencing grade 3 or greater TEAEs during study treatment and follow-up will be reported. An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study. An assessment of severity grade will be made using the following 5 general categorical descriptors based on division of acquired immunodeficiency syndrome (AIDS) grading for AE severity assessment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death.	During study treatment and follow-up (From Week 1 up to Week 88)
Percentage of Participants Experiencing TEAEs	Percentage of participants experiencing TEAEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any event that begins or worsens in severity after initiation of study drug through to the end of study.	From Week 1 up to Week 88
Percentage of Participants with TB Relapses and Re-infections During the Treatment-free Follow-up Phase	Percentage of participants with TB relapses and re-infections during the treatment-free follow-up phase will be reported.	During the treatment-free follow-up phase (Up to 48 weeks)
Percentage of Participants Whose Isolates Develop Resistance to Bedaquiline and Other Drugs Used in the Regimen	Percentage of participants whose isolates develop resistance to bedaquiline and other drugs used in the regimen will be reported.	Up to Week 88

Collaborators and Investigators

• Sponsor: Beijing Chest Hospital
• Investigators: Principal Investigator: Mengqiu Gao, Beijing Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Anticipated): August 8, 2025
• Study Completion (Anticipated): August 8, 2025

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Multidrug-Resistant; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Linezolid; Levofloxacin; Ofloxacin; Cycloserine; Bedaquiline; Pyrazinamide; Clofazimine; Prothionamide
• Other Study ID Numbers: TMC207TBC4006 (Other Identifier: Janssen Research & Development LLC)

Drug and device information, study documents

• 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