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

Tuberculosis, Multidrug-Resistant Clinical Trial

— PROSPECT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05306223
• Other study ID #: TMC207TBC4006
• Secondary ID: TMC207TBC4006
• Status: Recruiting
• Phase: Phase 4
• Start date: May 10, 2022
• Est. completion date: August 8, 2025

Study information

• Verified date: January 2023
• Source: Beijing Chest Hospital
• Contact: Jingtao Gao, PhD
• Phone: +8610-89509131
• Email: jingtaogao[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 212
• Est. completion date: August 8, 2025
• Est. primary completion date: August 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• Bedaquiline
Bedaquiline uncoated tablets will be administered orally.
• Levofloxacin
Levofloxacin filmcoated will be administered orally
• Linezolid
Linezolid tablets will be administered orally
• Cycloserine
Cycloserine capsules will be administered orally.
• Clofazimine
Clofazimine capsules will be administered orally.
• Pyrazinamide
Pyrazinamide tablets will be administered orally.
• Protionamide
Protionamide enteric-coated tablets will be administered orally.

Locations

Country	Name	City	State
China	Beijing Chest Hospital	Beijing
China	The Eighth Medical Center of PLA General Hospital	Beijing
China	Changsha Central Hospital	Changsha
China	Public health clinical medical center of Chengdu	Chengdu
China	Chongqing Public Health Medical Center	Chongqing
China	The Pulmonary Hospital of Fuzhou in Fujian Province(The tuberculosis control and prevention Hospital of Fuzhou in Fujian Province)	Fuzhou
China	Guiyang Public Health Clinical Center	Guiyang
China	Anhui Chest Hospital	Hefei
China	Infectious Disease Hospital of Heilongjiang Province	Heilongjiang
China	Jiamusi Tumor Hospital	Jiamusi
China	Jiangxi Chest Hospital	Jiangxi
China	Shandong public health clinical center	Shandong
China	Shanghai Pulmonary Hospital	Shanghai
China	Shenyang Chest Hospital	Shenyang
China	Wuhan Pulmonary Hospital	Wuhan
China	Xi'an Chest Hospital	Xi'an
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chest Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants Experiencing All-cause Mortality	Percentage of participants experiencing all-cause mortality will be reported.	Up to Week 88
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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