Treatment-refractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
Conditions
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).
Interventions
DRUGBedaquiline
Participants will receive BDQ tablets only/
DRUGClarithromycin
Participants will receive CAM 400 or 500 mg twice a day.
DRUGEthambutol
Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram \[g\]) or 15 mg/kg once a day.
DRUGRifampicin
Participants will receive daily dose is 450 mg (maximum 600 mg) RFP capsule once a day.
DRUGRifabutin
Participants will receive daily dose of RBT 300 mg or 150 mg capsules once a day.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sputum Culture Conversion in Mycobacteria Growth Indicator Tube (MGIT) at Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sputum Culture Conversion in 7H11 Agar Media at Week 24 | 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. |
| 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 | 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. |
| 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 | Baseline (Day 1), 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. |
| 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 | 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 24 was reported. |
| 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 | — |
Countries
Japan, South Korea, Taiwan
Contacts
STUDY_DIRECTORJanssen Pharmaceutical K.K., Japan clinical Trials
Janssen Pharmaceutical K.K.
Participant flow
Pre-assignment details
Results are currently reported until the Week 24 cut-off. Results of remaining duration will be posted upon study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 10.45 |
| Age, Customized 59 years and under | 44 Participants |
| Age, Customized 60 to 69 years | 41 Participants |
| Age, Customized 70 years and over | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 129 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment JAPAN | 118 Participants |
| Region of Enrollment SOUTH KOREA | 3 Participants |
| Region of Enrollment TAIWAN | 5 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 65 |
| other Total, other adverse events | 29 / 64 | 42 / 65 |
| serious Total, serious adverse events | 2 / 64 | 4 / 65 |
Outcome results
None listed