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)
- Conditions
- Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
- Interventions
- Registration Number
- NCT04630145
- Lead Sponsor
- Janssen Pharmaceutical K.K.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 129
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB) Clarithromycin 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. Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB) Ethambutol 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. Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB Ethambutol 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. Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB Rifampicin 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. Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB) Bedaquiline 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. Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB Clarithromycin 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. Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB Rifabutin 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Sputum Culture Conversion in Mycobacteria Growth Indicator Tube (MGIT) at Week 24 Week 24 Percentage of participant with sputum culture conversion (defined as 3 consecutive negative sputum cultures taken at least 25 days apart) in MGIT at Week 24 will be assessed.
- Secondary Outcome Measures
Name Time Method Number of Participants with Visual Examination Abnormalities Up to Week 60 Number of participants with visual examination abnormalities (visual acuity testing, color discrimination, visual field testing, and fundoscopy and audiology) will be assessed.
Area Under the Plasma Concentration-time Curve From Time Zero to End of Dosing Interval (tau) (AUC [0-tau]) of Bedaquiline and its Metabolite M2 Day 1, Weeks 2, 8, 12, 24 and Week 48 AUC (0-tau) is area under the plasma concentration-time curve from time zero to end of dosing interval (tau).
Percentage of Participants with Sputum Culture Conversion in 7H10 or 7H11 agar media at Week 24 Up to Week 24 Percentage of participants with sputum culture conversion (defined as 3 consecutive negative sputum cultures taken at least 25 days apart) in 7H10 or 7H11 agar media at Week 24 will be assessed.
Time to Sputum Culture Conversion in MGIT up to Week 48 Up to Week 48 Sputum culture conversion is defined as 3 consecutive negative sputum cultures taken at least 25 days apart. Percentage of participants with sputum culture in 7H10 or 7H11 agar media at Week 24 will be assessed. Time to sputum culture conversion in MGIT up to Week 48 will be assessed.
Change From Baseline in Patient Reported Health Status on Total Score of SGRQ at Weeks 48 and 60 From baseline to Week 48 and Week 60 The SGRQ is a self-administered questionnaire that has been validated in participants with airways disease, specifically in participants with bronchiectasis. The SGRQ assesses health-related quality of life in participants with chronic pulmonary disease by evaluating 3 health domains: symptoms (distress caused by respiratory symptoms); activity (effects of disturbances on mobility and physical activity); and impacts (the effect of disease on factors such as employment, personal control of one's health, and need for medication). A composite total score is derived as the sum of domain scores for symptoms, activity, and impact (0 = best possible score and 100 = worst possible score). A within patient reduction from baseline in score of 4 units is generally recognized as a clinically meaningful improvement in quality of life.
Change From Baseline in Lung Function Parameters (Forced Vital Capacity) at Weeks 24, 48, and 60 At Weeks 24, 48, and 60 The lung function parameters including forced expiration volume will be assessed.
Change From Baseline in Lung Function Parameters (Inspiratory Capacity) at Weeks 24, 48, and 60 At Weeks 24, 48, and 60 The lung function parameters including Inspiratory Capacity will be assessed.
Number of Participants with Physical Examination Abnormalities Up to Week 60 Number of Participants with physical examination abnormalities (all body systems \[including height and body weight measurement\] and observation for skin events/reactions) will be assessed.
Change from Baseline in Patient-reported Health Status on Total Score of St. George's Respiratory Questionnaire (SGRQ) at Week 24 Baseline and Week 24 The SGRQ is a self-administered questionnaire that has been validated in participants with airways disease, specifically in participants with bronchiectasis. The SGRQ assesses health-related quality of life in participants with chronic pulmonary disease by evaluating 3 health domains: symptoms (distress caused by respiratory symptoms); activity (effects of disturbances on mobility and physical activity); and impacts (the effect of disease on factors such as employment, personal control of one's health, and need for medication). A composite total score is derived as the sum of domain scores for symptoms, activity, and impact (0 = best possible score and 100 = worst possible score).
Percentage of Participants with Sputum Culture Negativity in MGIT and 7H10 or 7H11 at each visit after Week 2 From Week 2 to Week 60 Percentage of participants with sputum culture negativity in MGIT and 7H10 or 7H11 at each visit after Week 2 will be assessed.
Number of Participants with 12-Lead Electrocardiogram (ECG) Abnormalities Up to Week 60 Number of participants with 12-Lead ECG Abnormalities will be assessed.
Minimum Plasma Concentration Between 0 Hour and the Dosing Interval (tau) (Ctrough) of Bedaquiline and its Metabolite M2 Day 1, Weeks 2, 8, 12, 24 and Week 48 Ctrough is the minimum plasma concentration between 0 hour and dosing interval (tau).
Percentage of Participants with Sputum Culture Conversion in MGIT and 7H10 or 7H11 agar media at Week 48 and Week 60 Up to Week 48 and Week 60 Percentage of participants with sputum culture conversion (defined as 3 consecutive negative sputum cultures taken at least 25 days apart) in MGIT and 7H10 or 7H11 agar media at Week 48 and Week 60 will be assessed.
Number of Participants with Adverse Events (AE) Up to Week 60 An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
Number of Participants with Clinical Laboratory Abnormalities Up to Week 60 Number of participants with clinical laboratory abnormalities (Hematology, Clinical chemistry, and Urinalysis) will be assessed.
Number of Participants with Vital Signs Abnormalities Up to Week 60 Number of participants with vital signs abnormalities (body temperature \[axillary\], heart rate, respiratory rate, oxygen saturation, blood pressure \[systolic and diastolic\]) will be assessed.
Maximum Plasma Concentration (Cmax) of Bedaquiline and its Metabolite M2 Day 1, Weeks 2, 8, 12, 24 and Week 48 Cmax is defined as maximum observed analyte concentration.
AUC (0-tau) of Clarithromycin and its Metabolite 4-OH CAM Day 1, Weeks 2, 8, 12 and 24 AUC (0-tau) is area under the plasma concentration-time curve from time zero to end of dosing interval (tau).
Time to Positivity in MGIT up to Week 48 Up to Week 48 Time to positivity in MGIT up to week 48 will be assessed.
Percentage of Participants who Undergo a Change in Their Mycobacterium Avium Complex-lung Disease (MAC-LD) Treatment Regimen by Week 24 and by Week 48 in Group A and by Week 60 in Group B Week 24 and Week 48 (Group A) and by week 60 (Group B) Percentage of participants who undergo a change in their MAC-LD treatment regimen will be assessed.
Change From Baseline in Lung Function Parameters (Functional Residual Capacity and Total Lung Capacity) at Weeks 24, 48, and 60 At Weeks 24, 48, and 60 The lung function parameters including functional residual capacity and total lung capacity will be assessed.
C (0-trough) of Clarithromycin and its Metabolite 4-OH CAM Day 1, Weeks 2, 8, 12 and 24 Ctrough is the minimum plasma concentration between 0 hour and dosing interval (tau).
Cmax of Clarithromycin and its Metabolite 4-OH CAM Day 1, Weeks 2, 8, 12 and 24 Cmax is defined as maximum observed analyte concentration.
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Trial Locations
- Locations (55)
Shimonoseki City Hospital
🇯🇵Yamaguchi, Japan
National Hospital Organization Himeji Medical Center
🇯🇵Himeji, Japan
Kinki-chuo Chest Medical Center
🇯🇵Sakai, Japan
Hokkaido Medical Center
🇯🇵Sapporo Nishi-Ku, Japan
National Hospital Organization Tenryu Hospital
🇯🇵Hamamatue, Japan
St. Luke's International Hospital
🇯🇵Chuo ku, Japan
Saitama Prefectural Cardiovascular and Respiratory Center
🇯🇵Kumagaya, Japan
Gifu Prefectural General Medical Center
🇯🇵Gifu, Japan
Seirei Hamamatsu General Hospital
🇯🇵Hamamatsu, Japan
Matsunami Health Promotion Clinic
🇯🇵Hashimagun Kasamatsucho, Japan
National Hospital Organization Kyoto Medical Center
🇯🇵Kyoto, Japan
Kobe City Medical Center West Hospital
🇯🇵Kobe Nagata-Ku, Japan
Rakuwakai Otowa Hospital
🇯🇵Kyoto, Japan
National Center for Global Health and Medicine
🇯🇵Shinjuku City, Japan
Matsunami General Hospital
🇯🇵Hashima-gun, Japan
Saitama Medical University Hospital
🇯🇵Iruma-gun, Japan
National Hospital Organization Minami Kyoto Hospital
🇯🇵Joyo, Japan
Fukujuji Hospital
🇯🇵Kiyose, Japan
National Hospital Organization Fukuoka Higashi Medical Center
🇯🇵Koga, Japan
Fukuoka University Chikushi Hospital
🇯🇵Chikushino-shi, Japan
Fukui Prefectural Hospital
🇯🇵Fukui-shi, Japan
Hamamatsu Rosai Hospital
🇯🇵Hamamatsu-shi, Japan
National Hospital Organization Kochi National Hospital
🇯🇵Kochi, Japan
Matsusaka Municipal Hospital
🇯🇵Matsusaka, Japan
Musashino Red Cross Hospital
🇯🇵Musashino, Japan
Nagaoka Red Cross Hospital
🇯🇵Nagaoka, Japan
National Hospital Organization Omuta Hospital
🇯🇵Omuta, Japan
Tokyo Shinagawa Hospital
🇯🇵Shinagawa-ku, Japan
JRC Wakayama Medical Center
🇯🇵Wakayama, Japan
Saitama City Hospital
🇯🇵Saitama-shi, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya-shi, Japan
Kojunkai Daido Clinic
🇯🇵Nagoya, Japan
National Hospital Organization Nishiniigata Chuo Hospital
🇯🇵Niigata, Japan
National Hospital Organization Sagamihara National Hospital
🇯🇵Sagamihara, Japan
Tohoku Medical And Pharmaceutical University Hospital
🇯🇵Sendai, Japan
National Hospital Organization Nara Medical Center
🇯🇵Shichijo, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Japan
Nagano Prefectural Shinshu Medical Center
🇯🇵Suzaka, Japan
National Hospital Organization Ibarakihigashi
🇯🇵Tokai-mura, Japan
National Hospital Organization Tokyo Medical Center
🇯🇵Tokyo, Japan
National Hospital Organization Tokyo National Hospital
🇯🇵Tokyo, Japan
National Hospital Organization Ehime Medical Center
🇯🇵Toon, Japan
National Hospital Organization Osaka Toneyama Medical Center
🇯🇵Toyonaka-shi, Japan
Toyota Memorial Hospital
🇯🇵Toyota-shi, Japan
Toyota Kosei Hospital
🇯🇵Toyota, Japan
Kanagawa Cardiovascular And Respiratory Center
🇯🇵Yokohama, Japan
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
The Catholic University of Korea, Incheon St. Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan