A Study of Bedaquiline Administered as Part of a Treatment Regimen With Clarithromycin and Ethambutol in Adult Patients With Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)

Treatments: Drug: Ethambutol; Drug: Rifabutin; Drug: Rifampicin; Drug: Bedaquiline; Drug: Clarithromycin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04630145

TMC207NTM3002 (Other Identifier)

CR108897

Details and patient eligibility

About

The purpose of the study is to evaluate the efficacy of bedaquiline (BDQ) compared with rifamycin when administered as part of a treatment regimen with clarithromycin (CAM) and ethambutol (EB) in adult participants with treatment-refractory Mycobacterium avium complex-lung disease (MAC-LD) at Week 24 for microbiological assessment in mycobacteria growth indicator tube (MGIT).

Enrollment: 129 patients

Sex: All

Ages: 20 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has body weight greater than or equal to (>=) 40 kilograms (kg) at screening and on Day 1
• Has radiological evidence consistent with nontuberculous mycobacterial lung disease (NTM-LD) based on a chest Computed Tomography (CT) scan taken within 6 months prior to screening or at screening
• Has at least 2 positive sputum cultures of Mycobacterium avium complex (MAC) (sputum cultures to be taken at least 4 weeks apart): one obtained within 12 months prior to screening, which was documented while being treated for Mycobacterium avium complex lung disease (MAC-LD) for a total of at least 6 months; and one at screening (by central microbiology laboratory)
• Received at least 6 months of consecutive MAC-LD treatment (at least 2 antibiotics for MAC, including a macrolide), that is either ongoing or has stopped within 12 months prior to screening
• No presence of cognitive dysfunction that would impact the completion of the patient reported outcome (PRO) assessments

Exclusion criteria

• Had previous exposure to bedaquiline (BDQ)
• Has active Tuberculosis (TB) disease
• Has cystic fibrosis, medically unstable respiratory disease (for example, chronic obstructive pulmonary disease, bronchiectasis, asthma)
• Has one or more cavities >=2 centimeter (cm) in diameter on a chest CT scan taken within 6 months prior to screening or at screening
• Treatment already includes an injectable/inhaled aminoglycoside within 3 months prior to screening or the investigator deems the participant to be a candidate for an injectable/inhaled aminoglycoside during screening period or at Day 1

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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129 participants in 2 patient groups

Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB)

Experimental group

Description:

Participants will receive BDQ 400 milligrams (mg) (4\*100 mg tablets) once daily (qd) from Week 1-2 (loading phase), BDQ 200 mg (2\*100mg tablets) bi-weekly (biw) from Week 3 to 48 (maintenance phase) and CAM 400 mg or 500 mg twice daily (2\*200 mg tablets) along with EB 500-750 mg or 15 mg/kg once a day or maximum daily dose of 1.0 gram for up to Week 48.

Treatment:

Drug: Clarithromycin

Drug: Bedaquiline

Drug: Ethambutol

Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB

Active Comparator group

Description:

Participants will receive maximum of 4 capsules of RFP 450 mg daily (or maximum daily dose of 600 mg), CAM 400 mg or 500 mg (2\*200 mg tablets) twice a day along with EB 500-750 mg daily or 15 mg/kg once a day or maximum daily dose of 1.0 gram for up to Week 48, followed by 2 capsules of RBT 300 mg or 150 mg once a day.

Treatment:

Drug: Clarithromycin

Drug: Rifampicin

Drug: Rifabutin

Drug: Ethambutol