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

Pulmonary Tuberculosis Clinical Trial

— INSPIRE-CODA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06081361
• Other study ID #: BJCH-202301
• Status: Recruiting
• Phase: Phase 3
• Start date: December 22, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Beijing Chest Hospital
• Contact: Wenjuan Nie, M.D.
• Phone: 010-89509331
• Email: 94642975[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: December 31, 2026
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Pulmonary Tuberculosis
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Bedaquiline
Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week
• Delamanid
Oral, 100mg bid
• Contezolid
Oral, 800mg bid
• Levofloxacin
Oral, 400mg qd for weight <50kg, 600-750mg qd for weight =50kg
• Moxifloxacin
Oral, 400mg qd
• Clofazimine
Oral, 100mg qd
• Linezolid
Oral, 600mg qd
• Cycloserine
Oral, 250mg bid
• Prothionamide
Oral, 600mg qd for weight <50kg, 600-800mg qd for weight =50kg
• Pyrazinamide
Oral, 1500mg qd for weight <50kg, 1750mg qd for weight =50kg
• Para-Aminosalicylic Acid
8000mg qd for weight <50kg, 10000mg qd for weight =50kg
• Ethambutol
750mg qd for weight <50kg, 1000mg qd for weight =50kg

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Chest Hospital	National Medical Center for Infectious Diseases

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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