Feasibility of the Application of a new Six-month Treatment for multidrug-resistant tuberculosis (MDR-TB) patients in France (FAST-MDR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Determine if BPaLM has non-inferior effectiveness at 18 months after study treatment start compared to the long, conventional MDR-TB regimens assessed in an historical cohort of patients treated in France in 2006-2022.

Secondary objectives 13

1. 1) Evaluate early markers of BPaLM effectiveness (endpoints: a) proportion of participants with a negative sputum culture at two months after study treatment start, and b) time to sputum culture conversion [2021 WHO definitions]);
2. 2) Determine if BPaLM has non-inferior effectiveness at 6 and 12 months after treatment start compared to the historical cohort at the end of treatment (endpoint: for BPaLM arm, treatment success at 6 months, and sustained treatment success at 12 months, without addition of any TB drug or >4 consecutive weeks treatment interruption or >4 weeks treatment prolongation; for historical cohort: treatment success [all according to 2021 WHO definitions])
3. 3) Compare the rate of post-treatment relapse in the BPaLM arm and in the historical cohort (endpoint: for BPaLM arm, proportion of participants with TB relapse at 12 and 18 months after study treatment start. For historical cohort: proportion of patients with TB relapse according to latest available post-treatment follow-up data)
4. 4) Identify factors associated with effectiveness of BPaLM at 18 months after study treatment start (endpoint: factors associated with effectiveness, as per the primary endpoint definition)
5. 5) Assess the safety of BPaLM at 12 and 18 months after study treatment start (endpoint: proportion of participants with any serious adverse event [US FDA definition] or any Grade 3 or higher adverse event [CTCAE Severity Scale v 5.0])
6. 6) Perform blood therapeutic drug monitoring (TDM) (kinetic curves, total and free drug concentrations) and minimal inhibitory concentration (MIC) measurement on participant strains for each drug in the regimen, and assess the correlation with effectiveness/safety of BPaLM (endpoint: multivariate models adjusting for MICs, strain lineage and patient factors to identify TDM measures associated, for each drug, with effectiveness, safety, and drug resistance acquisition)
7. 7) Compare the rate of acquisition of drug resistance of BPaLM arm at 12 and 18 months after study treatment start to the historical cohort at the end of treatment (endpoint: acquired drug resistance, compared to baseline, to any drug in the study regimen)
8. 8) Assess diagnostic delay and accuracy of genotypic DST for the identification of patients who are eligible for BPaLM, compared to phenotypic DST (endpoint: diagnostic delay and accuracy)
9. 9) Assess treatment adherence to the BPaLM regimen (endpoint: proportion of doses taken out of total expected doses)
10. 10) Measure the health-related quality of life of BPaLM-treated participants before, during and after the treatment (endpoint: Saint George's Respiratory questionnaire)
11. 11) Measure the satisfaction of study participants and health care workers at 12 months after study treatment start (endpoint: Likert scales)
12. 12) Assess the overall costs of BPaLM and compare it with those of the historical cohort (endpoint: economic evaluation)
13. 13) Randomize participants to one of two bedaquiline dosing strategies to describe and compare between the two groups: a) bedaquiline blood TDM results, b) effectiveness and c) safety (endpoint: bedaquiline population pharmacokinetics, safety and effectiveness endpoints as defined above)

Conditions and MedDRA coding

Patients diagnosed at the study sites with rifampicinresistant tuberculosis during the recruitment period will be evaluated for study inclusion.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1) Is 18 years old or more
2. 2) 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
3. 3) Is willing and able to give informed consent to be enrolled in the research project (signed or witnessed consent if the patient is illiterate)
4. 4) 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;
5. 5) Is affiliated to a social security system (as beneficiary) or has state medical aid (AME) or has an ongoing demand for AME or has an ongoing demand for an emergency medical care (dispositif de soins d'urgence, as applicable for tuberculosis)

Exclusion criteria 13

1. 1) Is unable to take oral drugs
2. 2) Has known allergies, hypersensitivity or intolerance or any other medical condition and contra indications to any drug of the regimen
3. 3) Unwilling to comply to study procedures, at the clinician appreciation
4. 4) 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
5. 5) Is taking or needs to take contraindicated medications in association with investigational medicinal products
6. 6) Has ≥500 msec QTcF interval on any ECG taken at screening or baseline visits, or has any cardiac risk factor for severe arrhythmia
7. 7) Has severe extrapulmonary TB, including meningo-encephalitis, brain abscess, osteo-arthritis, osteomyelitis
8. 8) Is concurrently participating in another trial of any medicinal product
9. 9) 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)
10. 10) 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
11. 11) Has peripheral neuropathy of grade 3 or 4 (CTCAE scale)
12. 12) Has any other condition (social or medical) which, in the opinion of the site investigator, would make the study participant unsafe
13. 13) Is known to be pregnant or is unwilling or unable to stop breastfeeding an infant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For BPaLM interventional arm: 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 or >4 weeks treatment prolongation. For the historical cohort: proportion of patients achieving treatment success (2021 WHO definitions).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Stanislas Quenard

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Stanislas Quenard

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications