BPaL Regimen in FQ Resistant MDR-TB

• Status: Not yet recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this study is to analyze the efficacy of a new regimen using Bedaquiline, Pretomanid, and Linezolid for 26 weeks (6 months) for the treatment of FQ-resistant MDR-TB through the clinical trial. The recently completed Zenix trial observed that lower doses and/or shorter durations of linezolid than 1200mg for 6 months appear to have high efficacy and improved safety. Therefore, the primary objective of this study is to analyze the effectiveness and safety of the BPaL regimen including modified dosing of linezolid for the patients with fluoroquinolone-resistant MDR-TB.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborators: Chonnam National University Hospital; Funded by Korea Disease Control and Prevent Agency; International Tuberculosis Research Center; Investigational drug(Pretomanid) supported by Viatris Pharmaceutical; Masan National Tuberculosis Hospital; Pusan National University Hospital; Samsung Medical Center; Seoul National University Hospital; Severance Hospital

Criteria

Inclusion Criteria:

1. At least 19 years old at enrolment

2. Bodyweight over 35Kg

3. If culture positive in sputum or bronchoscopy specimen within 3 months of screening and confirmed as MDR-TB in the rapid or conventional DST.

4. Confirmed as resistance to fluoroquinolones in rapid and/or genotypic DST

5. If tuberculosis is confirmed by chest radiologic imaging

Exclusion Criteria:

1. Uncontrolled DM

2. Extrapulmonary TB that would require treatment longer than would be usual for pulmonary TB

3. Less than 30 Karnofsky score at enrolment

4. BMI less than 17

5. Known severe allergy to any of the BPaL component drugs

6. Medical history of Glucose-galactose malabsorption, galactose intolerance, and Lapp lactase deficiency

7. HIV-positive

8. When the QTcF interval exceeds 500 msec on the electrocardiogram at baseline

9. Patients who are at risk of Torsade de Pointes due to underlying heart diseases such as heart failure or arrhythmia

10. For women of childbearing potential if the pregnancy test is positive, women who are breastfeeding or planning to become pregnant within 6 months of discontinuation/termination of treatment during the study, or who do not want contraception (i.e., oral and subcutaneous hormonal contraceptives, condoms, diaphragms, intrauterine device, or use of appropriate contraceptive methods including abstinence)

*Note: Double contraception (e.g., when a male uses a barrier contraceptive method such as a condom, a female partner uses a hormonal contraceptive or an additional contraceptive method such as an intrauterine device) is required while taking the study drug and up to 6 months after stopping/terminating the study drug. In particular, taking the study drug may affect the efficacy of hormonal contraceptives, and even if you are using only barrier contraception at the same time with your partner, you cannot be sure of preventing pregnancy, so it is necessary to maintain double contraception.

11. Men who plan to become pregnant during the study period or within 6 months of discontinuation/termination of treatment, or who do not wish to use double contraception or abstinence during this period.

12. Patients who have Grade 3 or 4 or higher peripheral neuritis, or Grade 1 or 2 with a high probability of progression to peripheral neuritis,

13. Current use of monoamine oxidase Inhibitor or used 2 weeks before treatment

14. Use of serotonergic antidepressant within 3 days of treatment

15. Any contraindication that may affect QTc interval (amiodarone, chloroquine, chlorpromazine, clarithromycin, haloperidol, etc.)

16. Any contraindication that may cause myelosuppression

17. Taking drugs that affect the cytochrome P450 enzyme within 30 days (quinidine, tyramine, ketoconazole, fluconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine, dextromethorphan, etc.)

18. Previously treated with Bedaquiline or Linezolid for more than 4 weeks

19. Abnormal value of a blood test at baseline:

• Hypokalemia, Hemoglobin < 8.0 g/dL, Platelet < 75,000/mm3, ANC < 1000/mm3

• AST or ALT > 3 X ULN, Total bilirubin >2.0 X ULN, Albumin < 3.2 mg/dL

• Serum creatinine > 2 X ULN, Serum calcium < LLN, Serum magnesium < LLN