The Safety and Efficacy of BDL(Bedaquiline Plus Delamanid Plus Linezolid) Regimen in Subjects With Pulmonary Infection of Multi-drug Resistant Tuberculosis (MDR-TB) or Rifampicin-Resistant Tuberculosis (RR-TB)

NCT06476210 | Recruiting Phase 4

• 1 other identifier: YNLX-2024-009
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

The goal of this investigator initiated trial (IIT) is to learn if a 6-9months BDL regimen (bedaquiline plus delamanid plus linezolid）works to treat adults with multi-drug resistant tuberculosis or rifampicin-resistant pulmonary tuberculosis, in the context of Pretomanid not available in China. It will also learn about the safety of BDL regimen. The main questions it aims to answer are:

1. 1.What is the percentage of participants with favorable treatment outcome at the end of treatment?
2. 2.What are the frequency and degree of AE and SAE associated with BDL regimen?

Conditions

Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (2)

• The efficacy outcome at the end of treatment

  The efficacy outcome of treatment: bacteriological positive patients completed the prescribed treatment course, demonstrating bacteriological response without evidence of treatment failure Notes: bacteriological outcome response:bacterial culture conversion to negative and no recurrence of positivity thereafter Bacteriological conversion refers to confirmed tuberculosis patients having two or more consecutive negative sputum culture results, with at least a 7-day interval between each Recurrence of positivity refers to two or more consecutive sputum cultures were positive after bacteriological conversion, with at least a 7-day interval between each

  Baseline (within 9 days before treatment initiation), weeks 1, 2, 4, 6, 8 of treatment, thereafter every 4 weeks until week 26(or 39 weeks for patients require prolonged treatment) during the intervention

• Frequency of any adverse events (AEs) and serious adverse events (SAEs) occurring during the treatment period

  Baseline (within 9 days before treatment initiation), weeks 1-16, 20 and 26 during the intervention

Secondary Outcomes (3)

• Incidence of patients have bacterial recurrence within 12 months after treatment completion

  3,6,9,12 months after the intervention

• Time for sputum culture conversion to stable negativity during treatment

  3,6,9,12 months after the intervention

• Proportion of patients who discontinued treatment due to adverse reactions or permanently unable to take the medication

  during the intervention

Study Arms (1)

BDL interventionv group

EXPERIMENTAL

Drug: BDL regimen

Interventions

BDL regimen DRUG

Drug:bedaquiline 100mg tablets Other Names: Bdq TMC-207 bedaquiline 400 mg once daily for 2 weeks then 200mg 3 times per week Drug:delamanid 50mg tablets Other Names: Dlm OPC-67683 delamanid 100mg 2 times daily Drug:linezolid Scored 600mg tablets Other Names: Lzd linezolid 600mg once daily

BDL interventionv group

Eligibility Criteria

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

You may qualify if:

• A patient with multi-drug resistant/rifampicin-resistant pulmonary tuberculosis (MDR/RR-TB) with recent laboratory evidence (culture or molecular testing) within the last two months
• Age 18 years above
• No prior use of neither bedaquiline, delamanid, linezolid, or use for less than 4 weeks
• Positive culture result for mycobacterial at baseline(regardless smear positive or negative). No anti-tuberculosis treatment received within one month.
• For patients who don't have baseline sputum culture results,positive sputum smear and no effective anti-tuberculosis treatment administered
• \. No history of respiratory failure or heart failure, and no clinically significant manifestations of arrhythmia, with a QTcF under 450ms
• Promise to adhere to the treatment and follow-up schedule, complete treatment monitoring, and promptly report adverse reactions to the responsible physician
• Voluntarily participate in this study and sign the informed consent form

You may not qualify if:

• According to DMID, peripheral neuropathy is classified as grade 3 or 4. Alternatively, participants with grade 1 or 2 neuropathy, which the investigator believes may progress/worsen during the study
• Elevation of ALT or AST ≥3 times the upper limit of normal, or elevation of total bilirubin and direct bilirubin ≥2 times the upper limit of normal
• Pregnant women or those who intent to pregnant during treatment
• Participants who have participated in other drug trials in the past three months
• Known congenital QT interval prolongation or any disease prolonging the QT interval, or QTc\>450 ms
• History of symptomatic arrhythmias or clinically relevant bradycardia
• Any cardiac disease that could precipitate arrhythmias, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart failure with decreased left ventricular ejection fraction
• History of known, untreated, persistent hypothyroidism
• Electrolyte disturbances, especially hypokalemia, hypocalcemia, or hypomagnesemia
• History of allergy or known allergic reactions to any investigational drug or related substances
• BMI\<17 kg/m2
• Karnofsky performance score under 50, or as determined by the principal investigator, the anticipated survival of the participant is not expected to exceed 6 months
• Participants expected to require surgical intervention following assessment of their pulmonary disease
• Withdrawal Criteria
• Serious adverse events caused by the intervention

Sponsors & Collaborators

• Beijing Chest Hospital: lead
• Public Health Clinical Medical Center of Chengdu: collaborator
• Wuhan Institute for Tuberculosis Control: collaborator
• Changsha Central Hospital: collaborator
• Anhui Chest Hospital: collaborator
• Hunan Chest Hospital: collaborator
• Shandong Public Health Clinical Center: collaborator

Study Sites (7)

Anhui Chest Hospital

Hefei, Anhui, 230000, China

NOT YET RECRUITING

Beijing Chest Hospital

Beijing, Beijing Municipality, 101149, China

RECRUITING

Wuhan Institute for Tuberculosis Control

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Changsha Central Hospital

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Hunan Chest Hospital

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Shandong Public Health Clinical Center

Jinan, Shandong, 250000, China

NOT YET RECRUITING

Public Health Clinical Meadical Center of Chengdu

Chengdu, Sichuan, 610000, China

NOT YET RECRUITING

Related Publications (15)

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MeSH Terms

Conditions

Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; 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

• Yuhong Liu, Ph.D

  Beijing Chest Hostal

  PRINCIPAL INVESTIGATOR

• Mengqiu Gao, Ph.D

  Beijing Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuhong Liu, Ph.D

CONTACT

86-13691187507; liuyuhong0516@126.com

Wei Shu, Master

CONTACT

86-18710016231; shuwei@bjxkyy.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: June 26, 2024
• Study Start: June 1, 2024
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

CN (7)