Tuberculosis
Conditions
Interventions
Group A:BJLLfx(M)/C: JDB0131 100mg BID + Bedaquiline + Linezolid + Levofloxacin (Moxifloxacin) / Clofazimine
Grooup B:BJLLfx(M)/C: JDB0131 200mg BID + Bedaquiline + Linezolid + Levofloxacin (Moxifloxacin) / Clofazimine
Group C:BDLLfx/C: Delamanid + Bedaquiline + Linezolid + Levofloxacin / Clofazimine
Sponsors
Beijing Chest Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
14 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age: 14 years old< = age< = 65 years old, male or female; 2. Weight: 40kg<=weight<=90kg; 3. Patients with clinically diagnosed pulmonary tuberculosis who have been confirmed to be resistant to rifampicin by drug susceptibility testing and can accept molecular drug susceptibility or phenotypic drug susceptibility test results within 3 months before enrollment; 4. Positive sputum acid-fast bacillus smear (at least once=2+ or 1+ twice), and imaging shows substantive lesions in the lungs; 5. If the patient is undergoing anti-tuberculosis therapy or using anti-tuberculosis drugs, agree to stop all anti-tuberculosis drug treatment in the previous stage of treatment and complete 7 days of washout; 6. Women of childbearing age who agree to use highly effective contraception throughout the study period and for at least 6 months after drug discontinuation, and male subjects whose partners are women of childbearing age must agree to use adequate contraceptive methods throughout the study period and for at least 6 months after drug discontinuation (see Appendix 1); 7. Fully understand the purpose and requirements of this trial, voluntarily sign the written informed consent form and agree to abide by the relevant provisions in the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Those who cannot use dramanib, bedaquiline, and linezolid for various reasons; 2. Use of delamanib, bedaquiline, or linezolid for more than 1 month (may be included if evidence of intolerance can be provided); 3. Patients with hematogenous disseminated tuberculosis or severe extrapulmonary tuberculosis as determined by the investigator; or patients with pulmonary tuberculosis who may need surgical treatment within 8 weeks as assessed by the investigator; 4. History of torsades de pointes or risk factors, including personal or family history of long QT syndrome, persistent hypothyroidism, bradycardia; 5. Those who have any of the following cardiovascular diseases or other conditions within 6 months before enrollment: 1) Myocardial infarction; 2) cardiac surgery or coronary revenation (coronary artery bypass grafting/percutaneous coronary endovascular plasty); 3) Unstable angina; 4) Congestive heart failure (New York Heart Association cardiac function class III or IV); 5) Transient ischemic attack or severe cerebrovascular disease; 6. Peripheral neuropathy CTCAE grade 3 or 4; Grade 1 or 2 peripheral neuropathy may progress/worsen during the study process as judged by the investigator; Patients with optic neuritis; 7. Those with a history of gastrointestinal surgery or resection that may affect the absorption and/or excretion of oral drugs; 8. Those who have any unstable or serious cardiovascular, renal, hepatic, hematological, tumor, endocrine, metabolic, psychiatric or rheumatic diseases judged by the investigator to be unsuitable for this trial; 9. Patients with a history of alcohol dependence or drug abuse within 6 months before screening, which in the opinion of the investigator may affect the safety of the subjects and affect the compliance of the trial; 10. Patients who have used other clinical trial investigational drugs within 3 months before dosing; 11. Concomitant use of drugs that cause bone marrow suppression; 12. Concomitant use of serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-serotonin, serotonin receptor agonists and other drugs; 13. Concomitant use of drugs that cause QT prolongation, such as: quinidine, procainamide, amiodarone, sotalol, etc.; 14. Chronic systemic corticosteroid therapy, cumulative use of more than 4 weeks within 3 months before enrollment; 15. Allergy to any trial study drug or related substances confirmed by the clinical judgment of the investigator; 16. Women who have a positive pregnancy test or are lactating during the screening period; 17. Patients with hepatitis B with three positive results, namely hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antibody (HBcAb); Positive hepatitis C virus (HCV) antibody and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal; Positive HIV antibody test; Positive syphilis antibody test and in the active stage of syphilis; 18. Any of the following laboratory tests: 1) Hemoglobin 3 times the upper limit of normal value; 4) Alanine aminotransferase (ALT) > 3 times the upper limit of normal value; 5) Serum total bilirubin (TBIL) >2 times the upper limit of normal value; 6) Serum creatinine (Cr) > 1.5 times the upper limit of normal value; 7) Serum amylase > 2 times the upper limit of normal. 19. The following abnormalities in electrocardiogram: 1) At least 2 QTcF intervals >450
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The sputum culture conversion rate (SCC, %) in all groups after 8 weeks of treatment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to sputum culture conversion in all groups after 8 weeks of treatment;Time to positivity (TTP) in all groups after 8 weeks of treatment;Incidence rates of adverse events and serious adverse events in all groups after 8 weeks of treatment;Pharmacokinetic characteristics of JDB0131; | — |
Countries
China
Contacts
Public ContactNaihui Chu
Beijing Chest Hospital, Capital Medical University
Outcome results
None listed