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)
A Study of Bedaquiline Administered as Part of a Treatment Regimen With Clarithromycin and Ethambutol in Adult Patients With Treatmentrefractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
Numaguchi Hirotaka
Janssen Pharmaceutical K.K.
3-5-2 Nishi-kanda, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Medical Information Center
Janssen Pharmaceutical K.K.
3-5-2 Nishi-kanda, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Not Recruiting
Jan. 20, 2021
Mar. 05, 2021
124
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
-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 creening
- 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
Bedaquiline
Participants will receive BDQ tablets only.
Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB)
Clarithromycin
Participants will receive CAM 400 mg or 500 mg twice a day.
Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB)
Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB
Ethambutol
Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram [g]) daily or 15 mg/kg once a day.
Group A: Beaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB)
Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB
Rifampicin
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
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
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.
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.
Change from Baseline in Patientreported 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 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.
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.
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.
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.
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.
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.
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.
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 noninvestigational) 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 noninvestigational) 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 12-Lead Electrocardiogram (ECG) Abnormalities
Up to Week 60
Number of participants with 12-Lead ECG Abnormalities 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.
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.
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.
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).
Area Under the Plasma Concentrationtime 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).
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.
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).
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).
Janssen Pharmaceutical K.K.
Tokyo Shinagawa Hospital IRB
6-3-22, Higashioi, Shinagawa-ku, Tokyo
info@tokyo-shinagawa.jp
Approval
Oct. 28, 2020
Yes
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
