Nontuberculous Mycobacterial (NTM) Lung Infections caused by Mycobacterium avium complex (MAC) that are refractory to treatment MedDRA version: 20.0 Level: PT Classification code 10058806 Term: Mycobacterium avium complex infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Liposomal Amikacin for Inhalation (LAI)
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: AMIKACIN SULFATE
CAS Number: 39831-55-5
Other descriptive name: Amikacin Sulfate
Co
Sponsors
Insmed Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are eligible to participate in the study if they meet all the following inclusion criteria: 1. have successfully completed the Month 6 and End of Treatment (EoT) visits in INS-212 2. have not achieved the INS-212 protocol definition of culture conversion (3 consecutive monthly negative sputum cultures) by Month 6 in INS-212 OR have experienced a relapse or recurrence (agar positive or more than 2 consecutive broth positive results after culture conversion has occurred) by Month 6 in INS-212 3. have demonstrated compliance with treatment regimen in INS-212, including LAI, if applicable 4. willing to adhere to multi-drug treatment regimen during the course of the study 5. female of child bearing potential agrees to practice an acceptable method of birth control (e.g., true abstinence [refraining from heterosexual intercourse during the entire study], hormonal or barrier methods, partner sterilization, or intrauterine device [IUD]) while participating in the trial. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for the duration of the study, and withdrawal are not acceptable methods of contraception. 6. the subject will provide written informed consent 7. willing to have serum and sputum specimens stored 8. able to comply with study drug use, study visits, and study procedures as determined by the Investigator Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 134 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: Subjects are not eligible to participate in the study if they meet any of the following criteria: 1. achieved culture conversion without relapse or recurrence in the INS-212 study by Month 6 2. early discontinuation (prior to Month 6 study visit) from INS-212 3. met any of the exclusion criteria of the INS-212 study, with the exception of the following: a. unable to perform the 6MWT b. prior exposure to LAI (including clinical study) c. in the opinion of the Investigator, patients who are not expected to survive the duration of the study d. active allergic bronchopulmonary mycosis or any other condition requiring chronic systemic corticosteroids at a dose greater than the equivalent of 10 mg/day of prednisone e. initiation of chronic therapy (e.g., high dose ibuprofen, inhaled anti-inflammatory agents including steroids, low dose maintenance steroids, rhDNase) 4. positive pregnancy test or lactation. All women of child bearing potential will be tested. Women not of child bearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile. 5. significant (as determined by the Investigator) hearing loss, vestibular dysfunction, or neuromuscular weakness where the potential risk of aminoglycoside toxicity outweighs the potential benefit 6. aspartate aminotransferase or alanine aminotransferase = 3 times the upper limit of normal (ULN) and/or total bilirubin = 2 times the ULN at their Month 6 study visit in INS-212 7. absolute neutrophil count =500/µL at their Month 6 study visit in INS-212 8. serum creatinine >2 times ULN at their Month 6 study visit in INS-212 9. current alcohol, medication abuse or illicit drug abuse 10. any condition that, in the opinion of the Investigator, interferes with ability to safely complete the study or adhere to study requirements 11. diagnosis of myasthenia gravis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary Objectives 1. To evaluate the number of subjects achieving culture conversion (3 consecutive monthly negative sputum cultures) by Month 12/EOT (end of treatment) 2. To evaluate the number of subjects achieving culture conversion by Month 6 3. To evaluate the time to culture conversion 4. To evaluate the change in the six-minute walk test (6MWT) distance at Month 6 and Month 12/EOT Exploratory Objectives 1. To assess subject-reported symptoms of NTM and change from Baseline in quality of life scores on the St George’s Respiratory Questionnaire (SGRQ) and quality of life scores on the SGRQ – Part II (Activities of Daily Living) at Month 6 and Month 12/EOT 2. To assess the change from Baseline in the EQ-5D-3L questionnaire subject-reported health outcomes at Month 6 and Month 12/EOT;Primary end point(s): PRIARY ENDPOINT - SAFETY The primary endpoint is the frequency of treatment-emergent adverse events (TEAEs), TEAEs leading to withdrawal from study, treatment-emergent serious adverse events (SAEs), AEs of special interest, clinically significant abnormal laboratory test results, and vital signs measurements.;Timepoint(s) of evaluation of this end point: From baseline until end of study.;Main Objective: To evaluate long term safety and tolerability of LAI (590 mg) administered once daily (QD) for up to 12 months in subjects who were refractory to standard multi-drug treatment and failed to convert in Study INS-212. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SECONDARY ENDPOINTS - EFFICACY 1. Proportion of subjects achieving culture conversion (3 consecutive negative monthly sputum cultures without relapse or recurrence) by Month 12/EoT 2. Proportion of subjects achieving culture conversion by Month 6 3. Time to culture conversion. The date of conversion is defined by the date of the first of at least 3 consecutive monthly culture specimens that are MAC negative. 4. The mean change from Baseline in 6MWT distance at Month 6 and Month 12/EOT EXPLORATORY ENDPOINTS - EFFICACY 1. The mean change from Baseline at Month 6 and Month 12/EOT in the overall SGRQ and SGRQ – Part II (Activities of Daily Living) 2. The mean change from Baseline at Month 6 and Month 12/EOT in the EQ 5D-3L 3. Radiological changes in CT scan at EoT, within a sub-set of subjects.;Timepoint(s) of evaluation of this end point: From baseline until end of study. | — |
Countries
Australia, Austria, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactTom Vanthienen
Insmed Inc.
Outcome results
None listed