Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France (FAST-MDR)

NCT07486024 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: FAST-MDR
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The FAST-MDR trial is an externally-controlled, multicentre trial with one prospective arm, evaluating the non-inferiority of the effectiveness of BPaLM in the interventional arm versus the effectiveness of the long, conventional regimen in a French historical cohort of MDR-TB patients (2006-2022). In light of recent WHO recommendations suggesting using BPaLM as a first choice for routine MDR-TB treatment and of the expected benefits of BPaLM over the standard treatment, there will be no internal comparator arm in the study.

Conditions

MDR-TB; Tuberculosis Multi Drug Resistant Active; Antibiotic Resistance; Mycobacterium Tuberculosis

Keywords

MDR-TB; BPaLM; Tuberculosis Multi Drug Resistant

Outcome Measures

Primary Outcomes (1)

• Effectiveness of BPaLM compared to conventional MDR-TB regimens

  Proportion of study participants achieving sustained treatment success at 18 months after study treatment start, according to 2021 WHO definitions, in the absence of permanent addition of any TB drug to the regimen or \>4 consecutive weeks treatment interruption. For the historical cohort: proportion of patients achieving treatment success (2021 WHO definitions)

  Day 0 to Month 18

Secondary Outcomes (22)

• Early markers of BPaLM effectiveness (proportion of participants)

  Day 0 to Day 60

• Early markers of BPaLM effectiveness (time to sputum culture conversion)

  Day 0 to month 18

• BPaLM non-inferior effectiveness

  Start to month 6

• BPaLM non-inferior effectiveness

  Start to month 12

• Rate of post-treatment relapse

  Start to month 12

Study Arms (2)

Bedaquiline - 400 mg

EXPERIMENTAL

Posology : 400 mg once daily for 2 weeks and then 200 mg thrice weekly for the remaining 22 weeks.

Drug: Bedaquiline Oral Tablet

Bedaquiline - 200 mg

EXPERIMENTAL

Posology : 200 mg once daily for 8 weeks and then 100 mg daily for the remaining 16 weeks.

Drug: Bedaquiline Oral Tablet

Interventions

Bedaquiline Oral Tablet DRUG

Bedaquiline will be given as 400 mg once daily for 2 weeks and then 200 mg thrice weekly for the remaining 22 weeks

Bedaquiline - 400 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is 18 years old or more
• Is affected by bacteriologically- or molecularly-confirmed tuberculosis, due to strains of M. tuberculosis resistant to rifampicin (with or without resistance to isoniazid) according to a rapid molecular test
• Is willing and able to give informed consent to be enrolled in the research project (signed or witnessed consent if the patient is illiterate)
• Patients seen in consultation or hospitalized in one of the centers involved for rifampicin-resistant TB, with screening results available and compatible within 14 days following consent signature;
• Is willing to use effective\* contraception: women with childbearing potential\*\* must agree to use effective contraception, unless their partner has had a vasectomy, for the duration of study treatment and up to 6 months after the end of study treatment; men who have not had a vasectomy must agree to use effective contraception for the duration of study treatment and up to 3 months after the end of study treatment;
• The following contraception methods are considered effective, according to local regulation (CTFG recommendations, March 2024):
• Combined hormonal contraception (oestrogen + progestin)
• Progestin-only hormonal contraception
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner
• A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Is affiliated to a social security system (as beneficiary) or has state medical aid (AME) or has an ongoing demand for AMEor has an ongoing demand for an emergency medical care (dispositif de soins d'urgence, as applicable for tuberculosis)

You may not qualify if:

• Is unable to take oral drugs
• Has known allergies, hypersensitivity or intolerance or any other medical condition and contra indications to any drug of the regimen
• Unwilling to comply to study procedures, at the clinician appreciation
• Has proven or likely resistance to bedaquiline, clofazimine, linezolid, pretomanid or moxifloxacine, or has had exposure (for 30 days or more) in past five years to bedaquiline, clofazimine, delamanid, linezolid, or pretomanid
• Is taking or needs to take contraindicated medications in association with investigational medicinal products
• Has ≥500 msec QTcF interval on any ECG taken at screening or baseline visits, or has any cardiac risk factor for severe arrhythmia
• Has severe extrapulmonary TB, including meningo-encephalitis, brain abscess, osteo-arthritis, osteomyelitis
• Is concurrently participating in another trial of any medicinal product
• Is already on a MDR/RR-TB treatment regimen since 4 weeks or more, and has no need to change the treatment regimen (i.e. adverse events, treatment failure)
• Has significant and uncorrectable lab abnormalities at baseline: haemoglobin ≤7.9 g/dL, platelet count \<75 000/mm3; absolute neutrophil count \<1 000/ mm3; potassium \<3.0 mEq/L; serum creatinine \>3 x upper level of normality (ULN); alanine aminotransferase (ALT) ≥3 x ULN
• Has peripheral neuropathy of grade 3 or 4 (CTCAE scale)
• Has any other condition (social or medical) which, in the opinion of the site investigator, would make the study participant unsafe
• Is known to be pregnant or is unwilling or unable to stop breastfeeding an infant
• Individuals permanently legally incompetent adults, under judicial or administrative protection and vulnerable persons

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Viatris Inc.: collaborator

Study Sites (1)

Pitié-Salpêtrière Hospital - infectious and tropical diseases

Paris, France

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

bedaquiline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Central Study Contacts

Lorenzo GUGLIELMETTI, MD

CONTACT

01 40 77 97 46; lorenzo.guglielmetti@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study participants will be treated with a six-month treatment based on the combination of bedaquiline, linezolid, moxifloxacin and pretomanid (BPaLM), with the possible addition of clofazimine. All these drugs are routinely used for MDR-TB treatment, recommended by the WHO and other international guidelines, and approved by US FDA and EU EMA. The drugs will be given as follows: * Bedaquiline: 400 mg once daily for 2 weeks, then 200 mg thrice weekly; or 200 mg once daily for 8 weeks, then 100 mg once daily (dosing determined by randomization) * Clofazimine: 200 mg once daily for two weeks, then 100 mg once daily * Linezolid: 600 mg once daily * Moxifloxacin: 400 mg once daily * Pretomanid: 200 mg once daily

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: March 20, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): February 1, 2032
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)