BPaL(M) Regimen for the Treatment of MDR/RR-TB

Phase 4

Recruiting

• Conditions: Multidrug- and Rifampicin-resistant Tuberculosis
• Interventions: Drug: BPaL(M) regimen

• Registration Number: NCT05381194
• Lead Sponsor: Asan Medical Center

Brief Summary

The objective of this study is to analyze the efficacy of a new regimen using Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin for 24 weeks or Bedaquiline, Pretomanid, Linezolid for 26 weeks for the treatment of MDR/RR-TB through the clinical trial.

Detailed Description

The BPaL (Bedaquiline, Pretomanid, Linezolid) regimen has been proven effective for the treatment of Fluoroquinolone-resistant MDR-TB through studies such as the NixTB and ZeNix trials. In addition, the BPaLM regimen has been demonstrated to have excellent efficacy in RR-TB patients through the TB-PRACTECAL study. This study aims to analyze the efficacy of the BPaL(M) regimen in Korean MDR/RR-TB patients.

Study Timeline

• Study First Submitted: 2022-05-08
• Study First Submitted QC: 2022-05-14
• Study First Posted: 2022-05-19
• Study Start: 2022-12-13
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-13
• Last Update Posted: 2024-03-15
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. At least 19 years old at enrolment
2. Bodyweight over 35Kg
3. If rifampicin resistance is confirmed through molecular or phenotypic drug susceptibility testing conducted on sputum or bronchoscopy specimens within 3 months of screening
4. Chest radiological findings consistent with pulmonary tuberculosis

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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 BPaLM regimen drugs

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

7. HIV-positive

8. The QTcF interval exceeds 450 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm (investigational arm)	BPaL(M) regimen	BPaLM

Primary Outcome Measures

Name	Time	Method
A microbiological failure or clinical failure or relapse	until 12 months after the end of treatment	A microbiological failure or clinical failure or relapse during the treatment period and the 12-month follow-up period after end of treatment

Secondary Outcome Measures

Name	Time	Method
Proportion of culture-negative patients at specific times (weeks 4, 8, 12, 16, and 24 or 26)	26 weeks or 24 weeks	Frequency analysis of liquid and solid culture conversion at a specific time point
All-cause mortality	26 weeks or 24 weeks	Analyze the frequency and fraction of deaths and estimate the median using the Kaplan-Meier Method
Time to sputum culture conversion during the treatment period	26 weeks or 24 weeks	Analyze the time to liquid and solid culture conversion and estimate the median value using the Kaplan-Meier Method
Prescribed dose of Linezolid	26 weeks or 24 weeks	Analyze the actual dose of linezolid prescribed

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Songpa-gu, Korea, Republic of