A Randomized, Open Label, Multicenter Study of Liposomal Amikacin for Inhalation in Adult Patients who have Nontuberculous Mycobacterial Lung Infections caused by Mycobacterium avium complex that are refractory to treatment

Phase 1

• Conditions: ontuberculous Mycobacterial (NTM) Lung Infections caused by Mycobacterium avium complex (MAC) that are refractory to treatment; MedDRA version: 17.1 Level: PT Classification code 10058806 Term: Mycobacterium avium complex infection System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-005010-31-ES
• Lead Sponsor: Insmed Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-04-14
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 351

Inclusion Criteria

1. be male or female, 18 years or older
2. be continually positive for MAC on sputum culture while adhering to a multi-drug treatment regimen for a minimum duration of 6 months which is either ongoing or was stopped no more than 12 months before screening
3. be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest CT
4. have a MAC lung infection documented by at least 2 positive cultures (MAC or mixed infection with MAC as the dominant species) with at least one obtained within 6 months prior to and/or including screening.. Cultures may be obtained from sputum or bronchoscopy.
5. have a MAC-positive sputum at screening
6. be willing to adhere to multi-drug treatment regimen during the course of the study
7. be able to produce at least 3 mL of sputum or be willing to undergo an induction that produces at least 3 mL of sputum for mycobacteriology
8. female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)
9. provide written informed consent before performing any study related procedure
10. be willing to have serum specimens stored
11. be able to comply with study medication 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

1. patients with cystic fibrosis
2. patients whose MAC NTM infection is resistant to amikacin (as identified by mutation on RNA sequencing)
3. patients who are not able to perform the 6MWT
4. positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile.
5. active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 1 year before screening or anticipated during the study period
6. 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 within 3 months before screening
7. active pulmonary tuberculosis requiring treatment at screening
8. history of lung transplantation
9. initiation of chronic therapy (e.g., high-dose ibuprofen, inhaled anti-inflammatory agents including steroids, low dose maintenance steroids, recombinant human deoxyribonuclease [rhDNase]) within 28 days before Day 1.
10. administration of any investigational drug within 8 weeks before screening
11. prior exposure to LAI (including clinical study).
12. known hypersensitivity to aminoglycosides
13. use of inhaled or systemic aminoglycosides (e.g., tobramycin, amikacin, gentamicin, or streptomycin) within 28 days before Day 1
14. acquired and primary immunodeficiency syndromes
15. significant (as determined by the investigator) hearing loss, vestibular dysfunction, or neuromuscular weakness where the potential risk of aminoglycoside toxicity outweighs the potential benefit
16. aspartate aminotransferase or alanine aminotransferase ? 3 times the upper limit of normal (ULN) or total bilirubin ? 2 times the upper limit of normal (ULN) at screening
17. absolute neutrophil count ?500/?L at screening
18. serum creatinine >2 times ULN at screening
19. current alcohol, medication or illicit drug abuse
20. any condition that, in the opinion of the Investigator, interferes with ability to safely complete the study or adhere to study requirements
21. persons who have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified