Nontuberculous Mycobacterial Lung Infection NTM
Conditions
Interventions
ALIS 590 mg or ELC will be administered once daily (QD) by inhalation via
nebulization over approximately 6 minutes to up to 15 minutes. Study drug may
be administered around the same time each day,
Sponsors
Insmed Incorporated
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Subjects must satisfy all of the following criteria to be included in the study: 1. Male or female, >= 18 years of age (19 years or older in South Korea) 2. Current diagnosis of MAC lung infection (initial, second, or third infection event). MAC or mixed infection with MAC as the dominant species allowed, with MAC as the intended organism for treatment 3. Positive sputum culture for MAC within 6 months prior to Screening 4. Positive sputum culture for MAC at Screening 5. A chest computed tomography (CT) scan, read locally, within 6 months prior to Screening to determine presence and size of pulmonary cavities. Subjects who do not have a chest CT scan within 6 months prior to Screening will be required to obtain a chest CT scan, read locally, during Screening. 6. In the Investigator's opinion, documented respiratory signs/symptoms at Screening that are attributable to the current MAC lung infection 7. An average QOL-B respiratory domain score of
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be disqualified from entering the study: 1. Diagnosis of cystic fibrosis (CF) 2. History of more than 3 MAC lung infections 3. Received any mycobacterial antibiotic treatment for current MAC lung infection 4. Refractory MAC lung infection, defined as having positive MAC cultures while being treated with a multidrug mycobacterial antibiotic treatment regimen for a minimum of 6 consecutive months and no documented successful treatment, defined as negative sputum culture for MAC and cessation of treatment 5. Relapse of prior MAC lung infection, defined as positive sputum culture for MAC = 128 µg/mL at Screening 7. Evidence of any pulmonary cavity >= 2 cm in diameter, as determined by chest CT scan, read locally, within 6 months prior to Screening 8. Radiographic finding of new lobar consolidation, atelectasis, significant pleural effusion, or pneumothorax during routine clinical care within 2 months prior to Screening 9. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 1 year prior to Screening or anticipated during the study 10. Active pulmonary tuberculosis requiring treatment during Screening 11. Hospitalization for underlying lung disease during Screening 12. Acute pulmonary exacerbation (eg, COPD or bronchiectasis) requiring treatment with antibiotics, or corticosteroids (IV or oral), within 4 weeks prior to and during Screening 13. Predicted forced expiratory volume in 1 second (FEV1) = 3 times the upper limit of normal (ULN) or total bilirubin >= 1.5 times ULN at Screening 25. Absolute neutrophil count <= 500/µL at Screening 26. Serum c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint Findings on psychometric validation optimized and reported for: 1) Cross-sectional validation (modern psychometrics, internal consistency, concurrent validity, and known-groups validity) at Baseline. 2) Test-retest reliability between Screening and Baseline among subjects reporting no change on Patient Global Impression of Severity (PGI-S) between Screening and Baseline. PGI-S anchors will be PRO specific, with a respiratory and fatigue PGI-S applied to the Quality of Life - Bronchiectasis (QOL-B) respiratory domain and Patient-Reported Outcome Measurement Information System - Fatigue-Short Form 7a (PROMIS F-SF 7a), respectively. 3) Within-subject meaningful change estimated via anchor-based methods and validated via empirical cumulative distribution functions (eCDFs) and probability density functions (ePDFs) between Baseline and End of Study (EOS) (Month 7). | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving culture conversion by Month 6 (negative cultures for MAC at Month 5 and Month 6). Change from Baseline to Month 7 in respiratory symptom score. Change from Baseline to Month 7 in fatigue symptom score. Time to culture conversion (first of 2 consecutive negative cultures) of Baseline to EOT assessments. Time to first negative culture of Baseline to EOT assessments. Proportion of subjects who develop a MAC isolate with amikacin MIC >= 128 µg/mL at more than 1 visit at any timepoint during the study. Proportion of subjects who achieved culture conversion and subsequently have at least 1 MAC positive culture in agar media or positive cultures in broth media in at least 2 consecutive visits that is the same species and genome as cultured at Screening/Baseline. Proportion of subjects who achieved culture conversion and subsequently have at least 1 MAC positive culture in agar media or positive cultures in broth media in at least 2 consecutive visits that is different than cultured at Screening/Baseline (different species or same species but different genome). Incidence and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) and other safety variables (eg, vital signs, physical examination, clinical laboratory values) from Baseline through the end of study (EOS). | — |
Countries
Netherlands
Outcome results
None listed