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)

NCT04630145 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CR108897TMC207NTM3002
• Study Type: interventional
• Target: 129
• Locations: 3 countries
• Sites: 55

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• Number of Participants With Sputum Culture Conversion in 7H11 Agar Media at Week 24

  At week 24

• Change From Baseline in Patient Reported Health Status on Total Score of St. George's Respiratory Questionnaire (SGRQ) at Week 24

  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

Study Arms (2)

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

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Ethambutol

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

ACTIVE COMPARATOR

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; Drug: Ethambutol; Drug: Rifampicin; Drug: Rifabutin

Interventions

Bedaquiline DRUG

Participants will receive BDQ tablets only/

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

Clarithromycin DRUG

Participants will receive CAM 400 or 500 mg twice a day.

Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB); Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB

Ethambutol DRUG

Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram \[g\]) or 15 mg/kg once a day.

Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB); Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB

Rifampicin DRUG

Participants will receive daily dose is 450 mg (maximum 600 mg) RFP capsule once a day.

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

Rifabutin DRUG

Participants will receive daily dose of RBT 300 mg or 150 mg capsules once a day.

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

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (55)

Fukuoka University Chikushi Hospital

Chikushino-shi, 818-8502, Japan

Location

St. Luke's International Hospital

Chūōku, 104 8560, Japan

Location

Fukui Prefectural Hospital

Fukui-shi, 910-0846, Japan

Location

National Hospital Organization Ibarakihigashi

Funaishikawa, 319-1113, Japan

Location

Gifu Prefectural General Medical Center

Gifu, 500-8717, Japan

Location

Hamamatsu Rosai Hospital

Hamamatsu, 430-8525, Japan

Location

Seirei Hamamatsu General Hospital

Hamamatsu, 430-8558, Japan

Location

National Hospital Organization Tenryu Hospital

Hamamatue, 434-8511, Japan

Location

Matsunami General Hospital

Hashima-gun, 501-6062, Japan

Location

Matsunami Health Promotion Clinic

Hashimagun Kasamatsucho, 501-6062, Japan

Location

National Hospital Organization Himeji Medical Center

Himeji, 670-8520, Japan

Location

Saitama Medical University Hospital

Iruma-gun, 350-0495, Japan

Location

National Hospital Organization Minami Kyoto Hospital

Jōyō, 610-0113, Japan

Location

Fukujuji Hospital

Kiyose, 204-0022, Japan

Location

Kobe City Medical Center West Hospital

Kobe Nagata-Ku, 653-0013, Japan

Location

National Hospital Organization Kochi National Hospital

Kochi, 780-8077, Japan

Location

National Hospital Organization Fukuoka Higashi Medical Center

Koga, 811-3195, Japan

Location

Saitama Prefectural Cardiovascular and Respiratory Center

Kumagaya, 360-0197, Japan

Location

Rakuwakai Otowa Hospital

Kyoto, 607-8062, Japan

Location

National Hospital Organization Kyoto Medical Center

Kyoto, 612-8555, Japan

Location

Matsusaka Municipal Hospital

Matsusaka, 515-8544, Japan

Location

Musashino Red Cross Hospital

Musashino, 180-8610, Japan

Location

Nagaoka Red Cross Hospital

Nagaoka, 940-2085, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Kojunkai Daido Clinic

Nagoya, 457-8511, Japan

Location

National Hospital Organization Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

National Hospital Organization Nishiniigata Chuo Hospital

Niigata, 950-2085, Japan

Location

National Hospital Organization Omuta Hospital

Omuta, 837-0911, Japan

Location

National Hospital Organization Sagamihara National Hospital

Sagamihara, 252-0392, Japan

Location

Saitama City Hospital

Saitama-shi, 336-8522, Japan

Location

Kinki-chuo Chest Medical Center

Sakai, 591-8555, Japan

Location

Hokkaido Medical Center

Sapporo Nishi-Ku, 063-0005, Japan

Location

Tohoku Medical And Pharmaceutical University Hospital

Sendai, 983-8512, Japan

Location

National Hospital Organization Nara Medical Center

Shichijō, 630-8053, Japan

Location

Tokyo Shinagawa Hospital

Shinagawa-ku, 140-8522, Japan

Location

National Center for Global Health and Medicine

Shinjuku, 162-8655, Japan

Location

Keio University Hospital

Shinjuku-ku, 160-8582, Japan

Location

Nagano Prefectural Shinshu Medical Center

Suzaka, 386-8610, Japan

Location

National Hospital Organization Tokyo Medical Center

Tokyo, 152-8902, Japan

Location

National Hospital Organization Tokyo National Hospital

Tokyo, 204-8585, Japan

Location

National Hospital Organization Osaka Toneyama Medical Center

Toyonaka-shi, 560-8552, Japan

Location

Toyota Kosei Hospital

Toyota, 470-0396, Japan

Location

Toyota Memorial Hospital

Toyota-shi, 471-8513, Japan

Location

National Hospital Organization Ehime Medical Center

Tōon, 791-0281, Japan

Location

JRC Wakayama Medical Center

Wakayama, 640 8558, Japan

Location

Shimonoseki City Hospital

Yamaguchi, 750-0041, Japan

Location

Kanagawa Cardiovascular And Respiratory Center

Yokohama, 236-0051, Japan

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

The Catholic University of Korea, Incheon St. Mary's Hospital

Incheon, 403-720, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 135-230, South Korea

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

MeSH Terms

Interventions

bedaquiline; Clarithromycin; Ethambutol; Rifampin; Rifabutin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ethylenediamines; Diamines; Polyamines; Amines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Global Medical Head Mycobacteria
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Pharmaceutical K.K., Japan clinical Trials

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 16, 2020
• Study Start: January 8, 2021
• Primary Completion: November 6, 2024
• Study Completion: November 14, 2025
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (4); TW (4); JP (47)