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)

A Phase 2/3, Multicenter, Randomized, Open-label, Active-controlled Study to Evaluate the Efficacy and Safety 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)

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).

Study Overview

• Status: Completed
• Conditions: Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
• Intervention / Treatment: Drug: Bedaquiline; Drug: Clarithromycin; Drug: Ethambutol; Drug: Rifampicin; Drug: Rifabutin

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chikushino-shi, Japan, 818-8502
    • Fukuoka University Chikushi Hospital
  • Chūōku, Japan, 104 8560
    • St. Luke's International Hospital
  • Fukui-shi, Japan, 910-0846
    • Fukui Prefectural Hospital
  • Funaishikawa, Japan, 319-1113
    • National Hospital Organization Ibarakihigashi
  • Gifu, Japan, 500-8717
    • Gifu Prefectural General Medical Center
  • Hamamatsu, Japan, 430-8558
    • Seirei Hamamatsu General Hospital
  • Hamamatsu, Japan, 430-8525
    • Hamamatsu Rosai Hospital
  • Hamamatue, Japan, 434-8511
    • National Hospital Organization Tenryu Hospital
  • Hashima-gun, Japan, 501-6062
    • Matsunami General Hospital
  • Hashimagun Kasamatsucho, Japan, 501-6062
    • Matsunami Health Promotion Clinic
  • Himeji, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Jōyō, Japan, 610-0113
    • National Hospital Organization Minami Kyoto Hospital
  • Kiyose, Japan, 204-0022
    • Fukujuji Hospital
  • Kobe Nagata-Ku, Japan, 653-0013
    • Kobe City Medical Center West Hospital
  • Kochi, Japan, 780-8077
    • National Hospital Organization Kochi National Hospital
  • Koga, Japan, 811-3195
    • National Hospital Organization Fukuoka Higashi Medical Center
  • Kumagaya, Japan, 360-0197
    • Saitama Prefectural Cardiovascular and Respiratory Center
  • Kyoto, Japan, 607-8062
    • Rakuwakai Otowa Hospital
  • Kyoto, Japan, 612-8555
    • National Hospital Organization Kyoto Medical Center
  • Matsusaka, Japan, 515-8544
    • Matsusaka Municipal Hospital
  • Musashino, Japan, 180-8610
    • Musashino Red Cross Hospital
  • Nagaoka, Japan, 940-2085
    • Nagaoka Red Cross Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Nagoya, Japan, 457-8511
    • Kojunkai Daido Clinic
  • Niigata, Japan, 950-2085
    • National Hospital Organization Nishiniigata Chuo Hospital
  • Omuta, Japan, 837-0911
    • National Hospital Organization Omuta Hospital
  • Sagamihara, Japan, 252-0392
    • National Hospital Organization Sagamihara National Hospital
  • Saitama-shi, Japan, 336-8522
    • Saitama City Hospital
  • Sakai, Japan, 591-8555
    • Kinki-chuo Chest Medical Center
  • Sapporo Nishi-Ku, Japan, 063-0005
    • Hokkaido Medical Center
  • Sendai, Japan, 983-8512
    • Tohoku Medical and Pharmaceutical University Hospital
  • Shichijō, Japan, 630-8053
    • National Hospital Organization Nara Medical Center
  • Shinagawa-ku, Japan, 140-8522
    • Tokyo Shinagawa Hospital
  • Shinjuku, Japan, 162-8655
    • National Center for Global Health and Medicine
  • Shinjuku-ku, Japan, 160-8582
    • Keio University Hospital
  • Suzaka, Japan, 386-8610
    • Nagano Prefectural Shinshu Medical Center
  • Tokyo, Japan, 152-8902
    • National Hospital Organization Tokyo Medical Center
  • Tokyo, Japan, 204-8585
    • National Hospital Organization Tokyo National Hospital
  • Toyonaka-shi, Japan, 560-8552
    • National Hospital Organization Osaka Toneyama Medical Center
  • Toyota, Japan, 470-0396
    • Toyota Kosei Hospital
  • Toyota-shi, Japan, 471-8513
    • Toyota Memorial Hospital
  • Tōon, Japan, 791-0281
    • National Hospital Organization Ehime Medical Center
  • Wakayama, Japan, 640 8558
    • JRC Wakayama Medical Center
  • Yamaguchi, Japan, 750-0041
    • Shimonoseki City Hospital
  • Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
• South Korea
  • Gwangju, South Korea, 61469
    • Chonnam National University Hospital
  • Incheon, South Korea, 403-720
    • The Catholic University of Korea, Incheon St. Mary's Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 135-230
    • Samsung Medical Center
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB); 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.	Drug: Bedaquiline; Participants will receive BDQ tablets only/; Drug: Clarithromycin; Participants will receive CAM 400 or 500 mg twice a day.; Drug: Ethambutol; Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram [g]) or 15 mg/kg once a day.
Active Comparator: Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB; 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.	Drug: Clarithromycin; Participants will receive CAM 400 or 500 mg twice a day.; Drug: Ethambutol; Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram [g]) or 15 mg/kg once a day.; Drug: Rifampicin; Participants will receive daily dose is 450 mg (maximum 600 mg) RFP capsule once a day.; Drug: Rifabutin; Participants will receive daily dose of RBT 300 mg or 150 mg capsules once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sputum Culture Conversion in Mycobacteria Growth Indicator Tube (MGIT) at Week 24	Number of participants with sputum culture conversion in MGIT at Week 24 was reported. Sputum culture conversion was defined as 3 consecutive negative sputum cultures taken at least 25 days apart.	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sputum Culture Conversion in 7H11 Agar Media at Week 24	Number of participants with sputum culture conversion in 7H11 agar media at Week 24 was reported. Sputum culture conversion was defined as 3 consecutive negative sputum cultures taken at least 25 days apart based on actual collection dates.	At week 24
Change From Baseline in Patient Reported Health Status on Total Score of St. George's Respiratory Questionnaire (SGRQ) at Week 24	SGRQ is a 50-item questionnaire with 76 weighted responses. It provides a total score and three component scores: Symptoms (distress caused by respiratory symptoms), Activity (physical activities that cause or are limited by breathlessness), and Impacts (social and psychological effects of the disease). The composite total score is derived from the 3 domain scores. Each domain score and the total score has a range of 0 to 100, with 0 indicating the best possible quality of life. An increase in score indicates worsening health.	Baseline (Day 1), Week 24
Percentage of Participants With Sputum Culture Conversion in MGIT at Week 48		At Week 48
Percentage of Participants With Sputum Culture Conversion in 7H10 or 7H11 Agar Media at Week 48		At Week 48
Percentage of Participants With Sputum Culture Negativity in MGIT		From Week 2 to Week 60
Percentage of Participants With Sputum Culture Negativity in 7H10 or 7H11 Agar Media		From Week 2 to Week 60
Time to Sputum Culture Conversion in MGIT up to Week 48		From baseline (Day 1) up to Week 48
Time to Positivity in MGIT up to Week 48		From baseline (Day 1) up to Week 48
Change From Baseline in Patient-Reported Health Status on Total Score of SGRQ at Weeks 48 and 60		Baseline (Day 1), Week 48 and Week 60
Change From Baseline in Lung Function Parameters at Week 24	Change from baseline in lung function parameters (Forced expiratory volume in one second, Forced vital capacity, Inspiratory capacity, Functional residual capacity, Total lung capacity) at Week 24 was reported.	Baseline (Day 1), Week 24
Change From Baseline in Lung Function Parameters at Weeks 48 and 60		Baseline (Day 1), Week 48 and Week 60
Percentage of Participants Who Underwent a Change in Their Mycobacterium Avium Complex-lung Disease (MAC-LD) Treatment Regimen by Week 24	Percentage of participants who underwent a change in their Mycobacterium avium Complex-lung disease (MAC-LD) treatment regimen by Week 24 was reported.	Baseline (Day 1) up to Week 24
Percentage of Participants Who Underwent a Change in Their Mycobacterium Avium Complex-lung Disease (MAC-LD) Treatment Regimen by Week 48 and Week 60		Baseline (Day 1), Week 48 and Week 60
Percentage of Participants With Sputum Culture Conversion in MGIT at Week 60		At Week 60
Percentage of Participants With Sputum Culture Conversion in 7H10 or 7H11 Agar Media at Week 60		At Week 60
Number of Participants With Treatment-emergent Adverse Events (TEAEs)		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Laboratory Tests		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Vital Signs		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Physical Examination		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Visual Examination		From Baseline (Day 1) up to Week 60
Number of Participants With Clinically Significant Changes in Audiology		From Baseline (Day 1) up to Week 60
Minimum Plasma Concentration Between 0 Hour and the Dosing Interval (Tau) (Ctrough) of BDQ and Its Metabolite M2		Day 1, Weeks 2, 8, 12, 24 and Week 48
Minimum Plasma Concentration Between 0 Hour and the Dosing Interval (Tau) (Ctrough) of Clarithromycin and Its Metabolite 4-OH CAM		Day 1, Weeks 2, 8, 12 and 24

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.
• Investigators: Study Director: Janssen Pharmaceutical K.K., Japan clinical Trials, Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2021
• Primary Completion (Actual): November 6, 2024
• Study Completion (Actual): November 14, 2025

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Lung Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Amines; Macrolides; Lactones; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Erythromycin; Polyketides; Ethylenediamines; Diamines; Polyamines; Rifabutin; Clarithromycin; Rifampin; Ethambutol; bedaquiline
• Other Study ID Numbers: CR108897; TMC207NTM3002 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

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