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)

Janssen Pharmaceutical K.K.129 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

129

Conditions

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

Interventions

Bedaquiline

Eligibility

Sex: ALLMin age: 20 YearsMax age: 79 Years

Medical Language ↔ Plain English

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

Locations (55)

Fukuoka University Chikushi Hospital

Chikushino-shi, Japan

St. Luke's International Hospital

Chūōku, Japan

Fukui Prefectural Hospital

Fukui-shi, Japan

National Hospital Organization Ibarakihigashi

Funaishikawa, Japan

Gifu Prefectural General Medical Center

Gifu, Japan

Hamamatsu Rosai Hospital

Outcomes

Primary Outcomes

Percentage of Participants with Sputum Culture Conversion in Mycobacteria Growth Indicator Tube (MGIT) at 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.

Time frame: Week 24

Secondary Outcomes

Percentage of Participants with Sputum Culture Conversion in 7H10 or 7H11 agar media at 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 frame: Up to Week 24

Change from Baseline in Patient-reported Health Status on Total Score of St. George's Respiratory Questionnaire (SGRQ) at 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).

Time frame: Baseline and Week 24

Percentage of Participants with Sputum Culture Conversion in MGIT and 7H10 or 7H11 agar media at 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.

Time frame: Up to Week 48 and Week 60

Percentage of Participants with Sputum Culture Negativity in MGIT and 7H10 or 7H11 at each visit after Week 2

Percentage of participants with sputum culture negativity in MGIT and 7H10 or 7H11 at each visit after Week 2 will be assessed.

Time frame: From Week 2 to Week 60

Time to Sputum Culture Conversion in MGIT 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.

Time frame: Up to Week 48

Time to Positivity in MGIT up to Week 48

Time to positivity in MGIT up to week 48 will be assessed.

Time frame: Up to Week 48

Change From Baseline in Patient Reported Health Status on Total Score of SGRQ at Weeks 48 and 60

Time frame: From baseline to Week 48 and Week 60

Change From Baseline in Lung Function Parameters (Forced Vital Capacity) at Weeks 24, 48, and 60

The lung function parameters including forced expiration volume will be assessed.

Time frame: At Weeks 24, 48, and 60

Change From Baseline in Lung Function Parameters (Inspiratory Capacity) at Weeks 24, 48, and 60

The lung function parameters including Inspiratory Capacity will be assessed.

Time frame: At Weeks 24, 48, and 60

Change From Baseline in Lung Function Parameters (Functional Residual Capacity and Total Lung Capacity) at Weeks 24, 48, and 60

The lung function parameters including functional residual capacity and total lung capacity will be assessed.

Time frame: At Weeks 24, 48, and 60

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

Percentage of participants who undergo a change in their MAC-LD treatment regimen will be assessed.

Time frame: Week 24 and Week 48 (Group A) and by week 60 (Group B)

Number of Participants with Adverse Events (AE)

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.

Time frame: Up to Week 60

Number of Participants with Clinical Laboratory Abnormalities

Number of participants with clinical laboratory abnormalities (Hematology, Clinical chemistry, and Urinalysis) will be assessed.

Time frame: Up to Week 60

Number of Participants with 12-Lead Electrocardiogram (ECG) Abnormalities

Number of participants with 12-Lead ECG Abnormalities will be assessed.

Time frame: Up to Week 60

Number of Participants with Vital Signs Abnormalities

Number of participants with vital signs abnormalities (body temperature \[axillary\], heart rate, respiratory rate, oxygen saturation, blood pressure \[systolic and diastolic\]) will be assessed.

Time frame: Up to Week 60

Number of Participants with Physical Examination Abnormalities

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.

Time frame: Up to Week 60

Number of Participants with Visual Examination Abnormalities

Number of participants with visual examination abnormalities (visual acuity testing, color discrimination, visual field testing, and fundoscopy and audiology) will be assessed.

Time frame: Up to Week 60

Maximum Plasma Concentration (Cmax) of Bedaquiline and its Metabolite M2

Cmax is defined as maximum observed analyte concentration.

Time frame: Day 1, Weeks 2, 8, 12, 24 and Week 48

Minimum Plasma Concentration Between 0 Hour and the Dosing Interval (tau) (Ctrough) of Bedaquiline and its Metabolite M2

Ctrough is the minimum plasma concentration between 0 hour and dosing interval (tau).

Time frame: Day 1, Weeks 2, 8, 12, 24 and Week 48

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

AUC (0-tau) is area under the plasma concentration-time curve from time zero to end of dosing interval (tau).

Time frame: Day 1, Weeks 2, 8, 12, 24 and Week 48

Cmax of Clarithromycin and its Metabolite 4-OH CAM

Cmax is defined as maximum observed analyte concentration.

Time frame: Day 1, Weeks 2, 8, 12 and 24

C (0-trough) of Clarithromycin and its Metabolite 4-OH CAM

Ctrough is the minimum plasma concentration between 0 hour and dosing interval (tau).

Time frame: Day 1, Weeks 2, 8, 12 and 24

AUC (0-tau) of Clarithromycin and its Metabolite 4-OH CAM

AUC (0-tau) is area under the plasma concentration-time curve from time zero to end of dosing interval (tau).

Time frame: Day 1, Weeks 2, 8, 12 and 24