Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort

NCT06649721 | Active Not Recruiting Phase 3

• 1 other identifier: INSPIRE-BDLL
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 34

Brief Summary

This is an investigational, prospective, multicenter, single-arm, open label trial. The goal of this clinical trial is to evaluate the efficacy and safety of a 6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), or BDLLfxC regimen, to treat rifampin-resistant pulmonary tuberculosis (RR-TB) in Chinese teenagers and adults (aged 12 years or above). The main questions it aims to answer are:

• Is BDLLfxC regimen effective to treat RR-TB in Chinese participants?
• Is BDLLfxC regimen safe in Chinese RR-TB participants? Participants will take BDLLfxC regimen to treat their RR-TB. There will be no additional hospital visits, laboratory tests or radiological examinations other than routine clinical practice.

Conditions

Drug-resistant Tuberculosis; Pulmonary Tuberculosis; Rifampin-resistant Tuberculosis

Keywords

Drug-resistant tuberculosis; BDLL; Chinese Population; Short regimen

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with favorable outcomes in both treatment and follow-up period

  Favorable outcome in treatment period (up to 28 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, 1. . Cured: complete at least 80% of total required dose per protocol, with negative culture results of last two sputum samples (collected 14 days apart) ; 2. . Treatment completed: complete at least 80% of total required dose per protocol, with NO negative culture results of last two sputum samples (collected 14 days apart); Favorable outcome in follow-up period (from end of treatment to 72 weeks after start of treatment): a participant's outcome will be defined as "favorable" if it meets any of the following below and has not been defined as "unfavorable" before, (1). Cured: sputum culture negative at 72 weeks from start of treatment; (2). Culture negative when last seen: loss to follow-up before 72 weeks, with negative sputum culture when last seen.

  Up to 72 weeks after start of treatment

Secondary Outcomes (3)

• Proportion of participants with grade 3 or 4 adverse effect

  Up to 72 weeks after start of treatment

• Proportion of participants with favorable outcomes in treatment period, follow-up period and prolonged follow-up period, respectively

  Up to 108 weeks after start of treatment

• Time to culture conversion

  Up to 72 weeks after start of treatment

Study Arms (1)

BDLL

EXPERIMENTAL

6-month all-oral regimen, consisting of Bedaquiline (BDQ, B), Delamanid (DLM, D), Linezolid (LZD, L), Levofloxacin (LFX) or Clofazimine (CFZ, C), as known as BDLLfxC or BDLL regimen

Drug: bedaquiline; Drug: delamanid; Drug: linezolid; Drug: Levofloxacin; Drug: Clofazimine

Interventions

bedaquiline DRUG

400 milligrams (mg) daily for 2 weeks(w), then 200mg three times a week for 22 weeks (w)

Also known as: BDQ, B

BDLL

delamanid DRUG

* for participants weighing up to 33.9 kilograms (kg): 50mg two times a day for 24w * for participants weighing 34kg or above: 100mg two times a day for 8w, then 200mg daily for 16w

Also known as: DLM, D

BDLL

linezolid DRUG

* for participants weighing up to 33.9kg: 450mg daily; * for participants weighing 34kg or above: 600mg daily; for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Also known as: LZD, L

BDLL

Levofloxacin DRUG

Only for participants with confirmed fluoroquinolone-susceptible TB or unknown fluoroquinolone susceptibility: * for participants weighing up to 33.9kg: 500mg daily * for participants weighing 34kg to 49.9kg: 750 daily * for participants weighing 50kg or above: 1000mg daily for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Also known as: LFX

BDLL

Clofazimine DRUG

Only for participants with confirmed fluoroquinolone-resistant TB or unknown fluoroquinolone susceptibility: 100mg daily, for 24w if a negative culture is obtained from sputum collected at 16w, or else for 36w

Also known as: CFZ, C

BDLL

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are willing to sign informed consent of this trial, those without capacity for civil conduct need their legal guardian to sign
• Participants (and their legal guardian if applicable) are willing to cooperate to complete all trial procedures
• Male or female, 12 years or older, weight ≥ 30kg
• Women with childbearing potential should not be pregnant, confirmed by a volunteered negative pregnancy test, and are willing to use effective contraceptive method from giving consent to 3 months after study treatment
• Men with childbearing potential must be willing to use condom or other effective contraceptive methods to avoid their sex partners from being pregnant
• Women in breastfeeding period must be willing to discontinue breastfeeding from giving consent to 3 months after study treatment
• Participants are willing to take HIV test, and willing to take appropriate antiretroviral therapy if positive

You may not qualify if:

• Previously use of Bedaquiline or Delamanid for at least 28 days
• Concomitant hematogenous disseminated tuberculosis, or severe pulmonary tuberculosis in investigator's opinion (including tuberculosis of the digestive system, osteoarticular tuberculosis or tuberculous meningitis)
• Currently using any drug that has been prohibited in the protocol
• History of allergic action to any of the study drugs
• Currently participating in any other clinical trials
• Cardiovascular risk at screening: (1) QTcF more than 480 milliseconds (ms); (2) History of clinically significant arrythmia, and at investigator's opinion, participation in this study will increase the risk; (3) Decompensated heart failure; (4) Grade 3 high blood pressure and the goals of treatment have not been reached; (5) Abnormal thyroid function; (6) Abnormal serum Ca, Mg or K level; (7) Other conditions with cardiovascular risks in investigator's opinion.
• History of optic neuropathy or peripheral neuropathy, and the investigator considers that the condition may progress or deteriorate by participating in the study, or inappropriate to participate
• Hepatic disorders at screening: (1) Active viral hepatitis: HBsAg positive or HBV DNA \>1000 CPs/mL, with elevated AST or ALT or HCV RNA positive; (2) Decompensated cirrhosis
• Renal disorders at screening: (1) Unstable or rapidly progressive renal disease; (2) Moderate / severe renal disfunction or end-stage renal disease (eGFR\< 60 mL/min/1.73 m2); (3) Serum creatinine ≥133 μmol/L(1.5 mg/mL) in men, or ≥124 μmol/L (1.4 mg/mL) in women
• Other abnormal laboratory test: (1) Hemoglobin \< 8.0g/dL; (2) Platelet \<75,000/mm3; (3) Absolute neutrophil count \<1000/mm3; (4) Aspartate transaminase (AST) or alanine aminotransferase (ALT) \>3×upper limit of normal (ULN); (5) Total bilirubin (TBil) \>2×ULN, or \>1.5×ULN together with abnormal AST or ALT; (6) Albumin \<30g/L
• The investigator considers that the participant is not able to complete the study process, or the participation is not safe.

Sponsors & Collaborators

• Huashan Hospital: lead
• Beijing Chest Hospital: collaborator

Study Sites (34)

Anhui Chest Hospital

Hefei, Anhui, China

Location

The 8th Medical Center of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Location

The Fourth People's Hospital of Nanning

Nanning, Guangxi, China

Location

Liupanshui Third People's Hospital

Liupanshui, Guizhou, China

Location

Hebei Chest Hospital

Shijiazhuang, Hebei, China

Location

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, China

Location

Infectious Disease Hospital of Heilongjiang Province

Harbin, Heilongjiang, China

Location

Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)

Jiamusi, Heilongjiang, China

Location

Harbin Chest Hospital

Harbin, Helongjiang, China

Location

Luoyang Center Hospital

Luoyang, Henan, China

Location

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, China

Location

Henan Chest Hospital

Zhengzhou, Henan, China

Location

Henan Infectious Disease Hospital

Zhengzhou, Henan, China

Location

Wuhan Pulmonary Hospital，Wuhan Tuberculosis Prevention and Control Institute

Wuhan, Hubei, China

Location

Changsha Central Hospital

Changsha, Hunan, China

Location

Hulunbuir Infectious Disease Hospital

Hulunbuir, Inner Mongolia, China

Location

The Second Hospital of Nanjing

Nanjing, Jiangsu, China

Location

Jiangxi Chest Hospital

Nanchang, Jiangxi, China

Location

Infectious Disease Hospital of Changchun

Changchun, Jilin, China

Location

Jilin Tuberculosis Hospital

Jilin, Jilin, China

Location

Shenyang Chest Hospital

Shenyang, Liaoning, China

Location

Xi'an Chest Hospital

Xi'an, Shaanxi, China

Location

Shandong Public Health Clinical Center, Shandong University

Jinan, Shandong, China

Location

Linyi People Hospital

Linyi, Shandong, China

Location

Qingdao Chest Hospital

Qingdao, Shandong, China

Location

Weifang No.2 People's Hospital

Weifang, Shandong, China

Location

Yantai Qishan Hospital

Yantai, Shandong, China

Location

Shanxi Medical University Affiliated Chest Hospital

Taiyuan, Shanxi, China

Location

Public Health Clinical Center of Chengdu

Chengdu, Sichuan, China

Location

Tianjin Haihe Hospital

Tianjin, Tianjin Municipality, China

Location

Wenzhou Central Hospital

Wenzhou, Zhejiang, China

Location

Beijing Chest Hospital

Beijing, China

Location

Huashan Hospital

Shanghai, China

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Interventions

bedaquiline; OPC-67683; Fumigant 93; Linezolid; Levofloxacin; Clofazimine

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

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenazines; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Infectious Disease Department

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 21, 2024
• Study Start: November 27, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (34)