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

March 13, 2024 updated by: Chu naihui, Beijing Chest Hospital

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

186

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wenjuan Nie, M.D.
  • Phone Number: 010-89509331
  • Email: 94642975@qq.com

Study Contact Backup

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • The 8th Medical Center of Chinese Pla General Hospital
        • Contact:
          • Jianqin Liang
        • Principal Investigator:
          • Jianqin Liang
      • Changsha, China
        • Recruiting
        • Changsha Central Hospital
        • Contact:
          • Yi Pei
      • Changsha, China
        • Recruiting
        • Hunan Province Chest Hospital
        • Contact:
          • Hengzhong Yi
      • Chongqing, China
        • Recruiting
        • Chongqing Public Heath Treatment Center
        • Contact:
          • Fuping Yang
      • Dalian, China
        • Recruiting
        • Dalian Public Health Center
        • Contact:
          • Chunkui Cai
      • Fuzhou, China
        • Not yet recruiting
        • Fuzhou Pulmonary Hospital of Fujian
        • Contact:
          • Xiaohong Chen
      • Guangzhou, China
        • Not yet recruiting
        • Guangzhou Chest Hospital
        • Contact:
          • Haobin Kuang
      • Haerbin, China
        • Recruiting
        • Heilongjiang Province center for tuberculosis Control and Prevention
        • Contact:
          • Long Jin
      • Haikou, China
        • Not yet recruiting
        • Second Affiliated Hospital of Hainan Medical University
        • Contact:
          • Guizhong Zhou
      • Hangzhou, China
        • Recruiting
        • Hangzhou Red Cross Hospital
        • Contact:
          • Qingshan Cai
      • Hefei, China
        • Recruiting
        • Anhui Chest Hospital
        • Contact:
          • Hua Wang
      • Hohhot, China
        • Recruiting
        • Second People's Hospital of Hohhot
        • Contact:
          • Xiangqian Yang
      • Jiamusi, China
        • Recruiting
        • Jiamusi Infectious Disease Hospital
        • Contact:
          • Chao Qiu
      • Jiamusi, China
        • Recruiting
        • Jiamusi Tumor Hospital
        • Contact:
          • Xiujie Li
      • Jilin, China
        • Recruiting
        • Jilin Tuberculosis Hospital
        • Contact:
          • Xiaoshuang Jiang
      • Linyi, China
        • Recruiting
        • People's Hospital of Linyi
        • Contact:
          • Peiying Liu
      • Nanjing, China
        • Not yet recruiting
        • Second Hospital of Nanjing
        • Contact:
          • Xia Zhang
        • Contact:
          • Xiangrong Zhang
      • Nanning, China
        • Recruiting
        • Fourth People's Hospital of Nanning
        • Contact:
          • Qingdong Zhu
      • Nanning, China
        • Recruiting
        • Guangxi Chest Hospital
        • Contact:
          • Aimei Liu
        • Contact:
          • Yan Liao
      • Shandong, China
        • Recruiting
        • Shandong Public Health Clinical Center
        • Contact:
          • Yu Xiong
      • Shanghai, China
        • Recruiting
        • National Medical Center for Infectious Disease
        • Contact:
        • Contact:
          • Feng Sun, PhD
      • Shaoxing, China
        • Recruiting
        • Affiliated Hospital of Shaoxing University
        • Contact:
          • Xiaotong Tao
      • Shenyang, China
        • Recruiting
        • Shenyang Chest Hospital
        • Contact:
          • Lian Shi
      • Shijiazhuang, China
        • Recruiting
        • Shijiazhuang Fifth Hospital
        • Contact:
          • Yanxiao Rong
          • Phone Number: 17732865996
      • Tianjin, China
        • Recruiting
        • Tianjin Haihe Hospital
        • Contact:
          • Junping Wu
      • Weifang, China
        • Recruiting
        • Second People's Hospital of Weifang
        • Contact:
          • Wenge Han
      • Wuhan, China
        • Recruiting
        • Wuhan Institute For Tuberculosis Control
        • Contact:
          • Juan Du
      • Xi'an, China
        • Recruiting
        • Xi'an Chest Hospital
        • Contact:
          • Fei Ren
      • Xiamen, China
        • Recruiting
        • First Affiliated Hospital of Xiamen Medical University
        • Contact:
          • Xiangyang Yao
      • Xinxiang, China
        • Recruiting
        • The First Affiliated Hospital of Xinxiang Medical University
        • Contact:
          • Junwei Cui
      • Zhengzhou, China
        • Recruiting
        • Henan Provincial Chest Hospital
        • Contact:
          • Ruixia Liang
      • Zunyi, China
        • Recruiting
        • Affiliated Hospital of Zunyi Medical University
        • Contact:
          • Ling Chen
        • Contact:
          • Zhaoqian Zong
      • Ürümqi, China
        • Recruiting
        • The 8th Affiliated Hospital of Xinjiang Medical University
        • Contact:
          • Keya Ru
    • Beijing
      • Beijing, Beijing, China, 101149
        • Recruiting
        • Beijing Chest Hospital affiliated to Capital Medical University
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • Hebei Chest Hospital
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150000
        • Recruiting
        • Harbin Chest Hospital
        • Contact:
    • Inner Mongolia
      • Hulunbuir, Inner Mongolia, China
        • Recruiting
        • Infectious Disease Hospital of Hulunbuir
        • Contact:
          • Fan Zhang
    • Shandong
      • Qingdao, Shandong, China, 266000
        • Not yet recruiting
        • Qingdao Chest Hospital
        • Contact:
          • yufeng Liu
        • Contact:
          • Phone Number: 13863985511
    • Shanxi
      • Taiyuan, Shanxi, China, 030000
        • Recruiting
        • Taiyuan Fourth People's Hospital
        • Contact:
          • quanhong Wang
          • Phone Number: 13934242762

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: from randomization to 24 months after
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
Time Frame: from randomization to 24 months after

Including

  1. Death;
  2. Treatment failure
  3. Lost-to-follow-up
  4. Treatment Discontinuation
  5. Ttreatment prolonging
  6. Still on treatment at the end of follow up
  7. Recurrence
from randomization to 24 months after
Time to culture conversion
Time Frame: from randomization to 24 months after
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
Time Frame: from randomization to 24 months after
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
Time Frame: 7d±3d after the first dose of contezolid
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

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Chest Hospital

Collaborators

National Medical Center for Infectious Diseases

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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