Innovating Shorter, All- Oral, Precised, Individualized Treatment Regimen for Rifampicin Resistant Tuberculosis：Contezolid, Delamanid and Bedaquiline Cohort (INSPIRE-CODA)

A Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of a Contezolid, Delamanid and Bedaquiline-Containing Short Regimen for the Treatment of Rifampicin-Resistant Pulmonary Tuberculosis

The goal of this clinical trial is to compare the efficacy and safety of a Contezolid and Delamanid-Containing short regimen to standard longer regimen in Rifampicin-resistant pulmonary tuberculosis (RR-TB). The main questions it aims to answer are:

• Is the efficacy of short regimen non-inferior to standard regimen?
• Is the short regimen safe enough to replace the standard regimen?

Participants will:

• Be given with either short or standard regimen for RR-TB treatment
• Be asked to complete the scheduled visit as planned.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Tuberculosis; Rifampicin-resistant Tuberculosis
• Intervention / Treatment: Drug: Bedaquiline; Drug: Delamanid; Drug: Contezolid; Drug: Levofloxacin; Drug: Moxifloxacin; Drug: Clofazimine; Drug: Linezolid; Drug: Cycloserine; Drug: Prothionamide; Drug: Pyrazinamide; Drug: Para-Aminosalicylic Acid; Drug: Ethambutol

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • The 8th Medical Center of Chinese PLA General Hospital
  • Changsha, China
    • Changsha Central Hospital
  • Changsha, China
    • Hunan Province Chest Hospital
  • Chongqing, China
    • Chongqing Public Heath Treatment Center
  • Dalian, China
    • Dalian Public Health Center
  • Fuzhou, China
    • Fuzhou Pulmonary Hospital of Fujian
  • Guangzhou, China
    • Guangzhou Chest Hospital
  • Haerbin, China
    • Heilongjiang Province center for tuberculosis Control and Prevention
  • Haikou, China
    • Second Affiliated Hospital of Hainan Medical University
  • Hangzhou, China
    • Hangzhou Red Cross Hospital
  • Hefei, China
    • Anhui Chest Hospital
  • Hohhot, China
    • Second People's Hospital of Hohhot
  • Jiamusi, China
    • Jiamusi Tumor Hospital
  • Jiamusi, China
    • Jiamusi Infectious Disease Hospital
  • Jilin, China
    • Jilin Tuberculosis Hospital
  • Linyi, China
    • People's Hospital of Linyi
  • Nanjing, China
    • Second Hospital of Nanjing
  • Nanning, China
    • Fourth People's Hospital of Nanning
  • Nanning, China
    • Guangxi Chest Hospital
  • Shandong, China
    • Shandong Public Health Clinical Center
  • Shanghai, China
    • National Medical Center for Infectious Disease
  • Shaoxing, China
    • Affiliated Hospital of Shaoxing University
  • Shenyang, China
    • Shenyang Chest Hospital
  • Shijiazhuang, China
    • Shijiazhuang Fifth Hospital
  • Tianjin, China
    • Tianjin Haihe Hospital
  • Weifang, China
    • Second People's Hospital of Weifang
  • Wuhan, China
    • Wuhan Institute for Tuberculosis Control
  • Xi'an, China
    • Xi'an Chest Hospital
  • Xiamen, China
    • First Affiliated Hospital of Xiamen Medical University
  • Xinxiang, China
    • The First Affiliated Hospital of Xinxiang Medical University
  • Zhengzhou, China
    • Henan Provincial Chest Hospital
  • Zunyi, China
    • Affiliated Hospital Of Zunyi Medical University
  • Ürümqi, China
    • The 8th Affiliated Hospital of Xinjiang Medical University
  • Beijing
    • Beijing, Beijing, China, 101149
      • Beijing Chest Hospital Affiliated to Capital Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Hebei Chest Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Chest Hospital
  • Inner Mongolia
    • Hulunbuir, Inner Mongolia, China
      • Infectious Disease Hospital of Hulunbuir
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Qingdao Chest Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Taiyuan Fourth People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Age ≥18y and <70y when signing informed consent;
2. Initial or re-treatment for pulmonary tuberculosis with:

1) MTB positive in sputum or bronchoalveolar lavage fluid culture at or within 3 months before screening, or MTB positive in molecular test at or within 3 months before screening, and; 2) recorded Rifampicin-resistance at or before screening; 3. Imaging (Chest X-ray or CT scan) proved pulmonary tuberculosis within 1 year before screening; 4. Never used BDQ, DLM or CZD, or the accumulative duration of any of the treatment is not more than 2 weeks 5. For women in childbearing age, negative in pregnancy test and effective contraceptive measures throughout study is required; 6. For men, effective contraceptive measures is required; 7. Willing to participate the study and sign informed consent.

Exclusion criteria:

1. The participant will be excluded by investigator based on the medical history or concomitant diseases such as serious metabolic disease, cardiovascular disease, hepatobiliary disease, renal disease, autoimmune disease, neuropsychiatric disorders, hematological disease, malignant neoplastic disease and so on; or the study will have negative impact on the well-being of the participant, or the participant is considered unable to complete the evaluation by investigator;
2. History of alcohol or drug abuse that the study is considered have negative impact on the well-being of the participant by investigator;
3. HIV positive;
4. Chronic hepatitis with HBsAg, HBeAg and anti-HBC antibody positive, or HBV-DNA>1000 CPs/mL with rising ALT/AST;
5. Allergic to or known hypersensitive to any of study drugs;
6. Extensive (or advanced) pulmonary TB disease: presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography;
7. Hematogenous disseminated pulmonary tuberculosis and serious extrapulmonary tuberculosis (such as tuberculosis in digestive system, urogenital system, osteoarticular tuberculosis, tuberculous meningitis);
8. With any of following risk factors for cardiovascular disease: 1) history of arrhythmia and on consequential treatment; 2) QTcF>500ms on ECG; 3) history of ventricular arrhythmia; 4) torsade de pointe with heart failure, hypokalemia or familial long Q-T syndrome; 5) other possible risk factor for arrythmia;
9. Previous or current optic nerve disorder that may progress or deteriorate during the study by investigator's consideration;
10. Was enrolled within 2 months before screening, or currently in other studies; except for those who participating observational study or in the post-treatment period;
11. Being considered unlikely to survive for more than 6 months by investigator;
12. BMI < 17kg/m2
13. May need surgical procedures based on the evaluation of pulmonary lesions;
14. May continuous use prohibited concomitant medications that is considered not suitable for the study by investigator;
15. Positive in pregnancy test or known pregnancy, breastfeeding, or plan to become pregnant during or within 6 months after the study treatment;
16. Abnormal laboratory test results: 1) Plasma potassium lower than lower limit of normal (LLN); 2) Hb < 8.0 g/dL； 3) platelet count <75,000/mm3； 4) WBC count<3000/mm3； 5）AST/ALT >3×ULN； 6）creatinine>2×ULN；7）total bilirubin>2×ULN, or >1.5×ULN，with abnormal AST or ALT; 8) Albumin < 30g/L

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: Short-Term Regimen; Intervention will be determined based on Fluoroquinolones(FQs) resistance.; For those sensitive to FQs: BDQ DLM CZD LFX(MFX) for 6 months; For those resistant to FQs: BDQ DLM CZD CFZ for 6 months	Drug: Bedaquiline; Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week; Other Names: BDQ; Drug: Delamanid; Oral, 100mg bid; Other Names: DLM; Drug: Contezolid; Oral, 800mg bid; Other Names: CZD; Drug: Levofloxacin; Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg; Other Names: LFX; Drug: Moxifloxacin; Oral, 400mg qd; Other Names: MFX; Drug: Clofazimine; Oral, 100mg qd; Other Names: CFZ
Active Comparator: Standard Regimen; Intervention will be determined based on Fluoroquinolones(FQs) resistance.; For those sensitive to FQs: BDQ LZD LFX(MFX) CS CFZ regimen for 6 months, then LFX(MFX) CS CFZ for 12 months; For those resistant to FQs: LFX(MFX) will be replaced by Pto, PZA, PAS or EMB	Drug: Bedaquiline; Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week; Other Names: BDQ; Drug: Levofloxacin; Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg; Other Names: LFX; Drug: Moxifloxacin; Oral, 400mg qd; Other Names: MFX; Drug: Clofazimine; Oral, 100mg qd; Other Names: CFZ; Drug: Linezolid; Oral, 600mg qd; Other Names: LZD; Drug: Cycloserine; Oral, 250mg bid; Other Names: CS; Drug: Prothionamide; Oral, 600mg qd for weight <50kg, 600-800mg qd for weight ≥50kg; Other Names: Pto; Drug: Pyrazinamide; Oral, 1500mg qd for weight <50kg, 1750mg qd for weight ≥50kg; Other Names: PZA; Drug: Para-Aminosalicylic Acid; 8000mg qd for weight <50kg, 10000mg qd for weight ≥50kg; Other Names: PAS; Drug: Ethambutol; 750mg qd for weight <50kg, 1000mg qd for weight ≥50kg; Other Names: EMB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Favourable outcome rate at 24 months after randomization	The proportion of participants with a favourable outcome. A participant's outcome will be classified as favourable if their last two sputum culture results are negative unless they have previously been classified as unfavourable. These two cultures must be taken on separate visits (with ≥28d interval); the latest of which not being earlier than month 23 from randomization.	from randomization to 24 months after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unfavourable outcome rate at 24 months after randomization	Including; Death;; Treatment failure; Lost-to-follow-up; Treatment Discontinuation; Ttreatment prolonging; Still on treatment at the end of follow up; Recurrence	from randomization to 24 months after
Time to culture conversion	Time from treatment initiation to first negative result in sputum culture confirmed by two consecutive cultures with an interval of ≥28d	from randomization to 24 months after
Grade 3 or higher adverse event rate	Proportion of participants experiencing at least one grade 3 or higher adverse event, or serious adverse event defined by the Division of AIDS severity criteria for adverse events	from randomization to 24 months after

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contezolid plasma concentration	To build the population PK model of contezolid with steady-state plasma concentration, measured by blood samples taken at four time points around one administration: ≤15min before and 1h±15min, 2h±15min, 3h±15min after. The index adiministration should be in 7d±3d after the first dose of contezolid.	7d±3d after the first dose of contezolid

Collaborators and Investigators

• Sponsor: Beijing Chest Hospital
• Collaborators: National Medical Center for Infectious Diseases

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: tuberculosis; delamanid; Rifampicin-resistant; short regimen; contezolid
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Enzyme Inhibitors; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Protein Synthesis Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Linezolid; Moxifloxacin; Clofazimine; Ethambutol; Bedaquiline; Levofloxacin; Cycloserine; Pyrazinamide; Aminosalicylic Acid; Prothionamide
• Other Study ID Numbers: BJCH-202301

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