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

The 6-month BPaL(M) Regimen for the Treatment of Patients With MDR/RR-TB: Multicenter, Single-arm, Operational Research, Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Multidrug- and Rifampicin-resistant Tuberculosis
• Intervention / Treatment: Drug: BPaL(M) regimen

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tae Sun Shim, MD, PhD; Phone Number: +82-2-3010-3892; Email: shimts@amc.seoul.kr

Study Locations

• Korea, Republic of
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of, 05505
      • Recruiting
      • Asan Medical Center
      • Contact: Tae Sun Shim, MD, PhD; Phone Number: +82-2-3010-3892; Email: shimts@amc.seoul.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single arm (investigational arm); BPaLM

Drug: BPaL(M) regimen; Patients diagnosed with MDR/RR-TB are initially assigned to the BPaLM regimen as a single-arm for treatment initiation. Afterward, if MDR/RR-TB is confirmed to be fluoroquinolone-resistant by molecular or phenotypic DST, the treatment is switched to the BPaL regimen (for 24 weeks). On the other hand, if MDR/RR-TB is confirmed to be fluoroquinolone-susceptible, treatment for MDR/RR-TB is maintained with the BPaLM regimen (for 26 weeks). The dosage of each medication is as follows: Bedaquiline 400mg/day for the 2 weeks, 200mg/TIW afterward; Pretomanid 200mg/day; Linezolid 600mg/day for the 9weeks, 300mg/day afterward; Moxifloxacin 400mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A microbiological failure or clinical failure or relapse	A microbiological failure or clinical failure or relapse during the treatment period and the 12-month follow-up period after end of treatment	until 12 months after the end of treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Samsung Medical Center; Pusan National University Hospital; Chonnam National University Hospital; Seoul National University Hospital; Ulsan University Hospital; The Catholic University of Korea; Severance Hospital; Soon Chun Hyang University; Chungbuk National University Hospital; Incheon St.Mary's Hospital; DongGuk University; National Medical Center, Seoul

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 8, 2022
• First Submitted That Met QC Criteria: May 14, 2022
• First Posted (Actual): May 19, 2022

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

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: BPaL(M)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No