Clinical trial NCT04630145: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 129
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Sputum Culture Conversion in Mycobacteria Growth Indicator Tube (MGIT) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants with Sputum Culture Conversion in 7H10 or 7H11 agar media at Week 24
timeFrame: Up to Week 24
measure: Change from Baseline in Patient-reported Health Status on Total Score of St. George's Respiratory Questionnaire (SGRQ) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants with Sputum Culture Conversion in MGIT and 7H10 or 7H11 agar media at Week 48 and Week 60
timeFrame: Up to Week 48 and Week 60
measure: Percentage of Participants with Sputum Culture Negativity in MGIT and 7H10 or 7H11 at each visit after Week 2
timeFrame: From Week 2 to Week 60
measure: Time to Sputum Culture Conversion in MGIT up to Week 48
timeFrame: Up to Week 48
measure: Time to Positivity in MGIT up to Week 48
timeFrame: Up to Week 48
measure: Change From Baseline in Patient Reported Health Status on Total Score of SGRQ at Weeks 48 and 60
timeFrame: From baseline to Week 48 and Week 60
measure: Change From Baseline in Lung Function Parameters (Forced Vital Capacity) at Weeks 24, 48, and 60
timeFrame: At Weeks 24, 48, and 60
measure: Change From Baseline in Lung Function Parameters (Inspiratory Capacity) at Weeks 24, 48, and 60
timeFrame: At Weeks 24, 48, and 60
measure: Change From Baseline in Lung Function Parameters (Functional Residual Capacity and Total Lung Capacity) at Weeks 24, 48, and 60
timeFrame: At Weeks 24, 48, and 60
measure: 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
timeFrame: Week 24 and Week 48 (Group A) and by week 60 (Group B)
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to Week 60
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to Week 60
measure: Number of Participants with 12-Lead Electrocardiogram (ECG) Abnormalities
timeFrame: Up to Week 60
measure: Number of Participants with Vital Signs Abnormalities
timeFrame: Up to Week 60
measure: Number of Participants with Physical Examination Abnormalities
timeFrame: Up to Week 60
measure: Number of Participants with Visual Examination Abnormalities
timeFrame: Up to Week 60
measure: Maximum Plasma Concentration (Cmax) of Bedaquiline and its Metabolite M2
timeFrame: Day 1, Weeks 2, 8, 12, 24 and Week 48
measure: Minimum Plasma Concentration Between 0 Hour and the Dosing Interval (tau) (Ctrough) of Bedaquiline and its Metabolite M2
timeFrame: Day 1, Weeks 2, 8, 12, 24 and Week 48
measure: 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
timeFrame: Day 1, Weeks 2, 8, 12, 24 and Week 48
measure: Cmax of Clarithromycin and its Metabolite 4-OH CAM
timeFrame: Day 1, Weeks 2, 8, 12 and 24
measure: C (0-trough) of Clarithromycin and its Metabolite 4-OH CAM
timeFrame: Day 1, Weeks 2, 8, 12 and 24
measure: AUC (0-tau) of Clarithromycin and its Metabolite 4-OH CAM
timeFrame: Day 1, Weeks 2, 8, 12 and 24
Other outcomes:
Locations:
city: Chikushino-shi
country: Japan
facility: Fukuoka University Chikushi Hospital
city: Chuo ku
country: Japan
facility: St. Luke's International Hospital
city: Fukui-shi
country: Japan
facility: Fukui Prefectural Hospital
city: Gifu
country: Japan
facility: Gifu Prefectural General Medical Center
city: Hamamatsu-shi
country: Japan
facility: Hamamatsu Rosai Hospital
city: Hamamatsu
country: Japan
facility: Seirei Hamamatsu General Hospital
city: Hamamatue
country: Japan
facility: National Hospital Organization Tenryu Hospital
city: Hashima-gun
country: Japan
facility: Matsunami General Hospital
city: Hashimagun Kasamatsucho
country: Japan
facility: Matsunami Health Promotion Clinic
city: Himeji
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Joyo
country: Japan
facility: National Hospital Organization Minami Kyoto Hospital
city: Kiyose
country: Japan
facility: Fukujuji Hospital
city: Kobe Nagata-Ku
country: Japan
facility: Kobe City Medical Center West Hospital
city: Kochi
country: Japan
facility: National Hospital Organization Kochi National Hospital
city: Koga
country: Japan
facility: National Hospital Organization Fukuoka Higashi Medical Center
city: Kumagaya
country: Japan
facility: Saitama Prefectural Cardiovascular and Respiratory Center
city: Kyoto
country: Japan
facility: Rakuwakai Otowa Hospital
city: Kyoto
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Matsusaka
country: Japan
facility: Matsusaka Municipal Hospital
city: Musashino
country: Japan
facility: Musashino Red Cross Hospital
city: Nagaoka
country: Japan
facility: Nagaoka Red Cross Hospital
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
city: Nagoya-shi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Nagoya
country: Japan
facility: Kojunkai Daido Clinic
city: Niigata
country: Japan
facility: National Hospital Organization Nishiniigata Chuo Hospital
city: Omuta
country: Japan
facility: National Hospital Organization Omuta Hospital
city: Sagamihara
country: Japan
facility: National Hospital Organization Sagamihara National Hospital
city: Saitama-shi
country: Japan
facility: Saitama City Hospital
city: Sakai
country: Japan
facility: Kinki-chuo Chest Medical Center
city: Sapporo Nishi-Ku
country: Japan
facility: Hokkaido Medical Center
city: Sendai
country: Japan
facility: Tohoku Medical And Pharmaceutical University Hospital
city: Shichijo
country: Japan
facility: National Hospital Organization Nara Medical Center
city: Shinagawa-ku
country: Japan
facility: Tokyo Shinagawa Hospital
city: Shinjuku City
country: Japan
facility: National Center for Global Health and Medicine
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
city: Suzaka
country: Japan
facility: Nagano Prefectural Shinshu Medical Center
city: Tokai-mura
country: Japan
facility: National Hospital Organization Ibarakihigashi
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo National Hospital
city: Toon
country: Japan
facility: National Hospital Organization Ehime Medical Center
city: Toyonaka-shi
country: Japan
facility: National Hospital Organization Osaka Toneyama Medical Center
city: Toyota-shi
country: Japan
facility: Toyota Memorial Hospital
city: Toyota
country: Japan
facility: Toyota Kosei Hospital
city: Wakayama
country: Japan
facility: JRC Wakayama Medical Center
city: Yamaguchi
country: Japan
facility: Shimonoseki City Hospital
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular And Respiratory Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea, Incheon St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan clinical Trials
role: STUDY_DIRECTOR
References: