A Randomized, Open Label, Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients with Nontuberculous Mycobacterial (NTM) Lung Infections caused by Mycobacterium avium complex (MAC) that are refractory to treatment
- Conditions
- Lung infectionMycobacterial Lung Infection1002844010024970
- Registration Number
- NL-OMON43943
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
1. be male or female, 18 years or older (20 years or older in Japan)
2.be positive for MAC on culture as defined in inclusion criterion No. 4 while being treated with a multi-drug treatment regimen (at least 2 antibiotics) for a minimum duration of 6 consecutive months that is either ongoing or was stopped no more than 12 months before Screening (exceptions to multi-drug treatment regimen for 6 consecutive months include treatment with doses or frequencies below those recommended by guidelines and/or short interruptions of therapy, both occurring due
to safety/tolerability issues)
3. be diagnosed with MAC NTM lung infection with evidence of underlying lung disease such as nodular bronchiectasis and/or fibrocavitary disease by chest radiography (CXR) or high-resolution
chest computed tomography. High resolution CT (HRCT) scan is preferred, if available
4. have a MAC lung infection documented by at least 2 positive cultures (MAC or mixed infection with MAC as the dominant species), consisting of at least one positive culture obtained within 6 months prior to Screening and one positive culture at Screening (cultures to be at least 1 month apart). 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 approximately 3 mL of sputum or be willing to undergo an induction that produces approximately 3 mL of sputum for mycobacteriology
8. 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, post-ovulation methods), declaration of abstinence for the duration of the study, and withdrawal are not acceptable methods of contraception.
9. the patient will 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 drug use, study visits, and study procedures as determined by the investigator
A patient with any of the following conditions must be excluded from this study:
1. patients with cystic fibrosis
2. patients whose MAC NTM infection is resistant to amikacin (as identified by MIC susceptibility > 64µg/ml)
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 with activity against MAC (e.g., amikacin, kanamycin, or streptomycin) within 28 days before Day 1
14. acquired and primary immunodeficiency syndromes and acquired immunodeficiency syndromes (e.g. HIV-positive patients regardless of CD4 counts)
15. significant (as determined by the Investigator) hearing loss, vestibular dysfunction, neuromuscular weakness or a diagnosis of myasthenia gravis 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
22. in the opinion of the Investigator, patients who are not expected to survive the duration of the study
23. patients with disseminated MAC infection
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the proportion of subjects achieving culture conversion<br /><br>(3 consecutive monthly negative sputum cultures) by Month 6 in the LAI arm<br /><br>compared to multi-drug regimen alone.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Change in 6MWT distance at Month 6 in the LAI arm compared to a multi drug<br /><br>regimen alone<br /><br>2. Proportion of subjects achieving culture conversion with durability after 3<br /><br>months off treatment in the LAI arm compared to a multi drug regimen alone<br /><br>3. Time to culture conversion in the LAI arm compared to a multi drug regimen<br /><br>alone by Month 6<br /><br>4. Proportion of subjects achieving culture conversion with sustainability at<br /><br>the EOT in the LAI arm compared to a multi drug regimen alone<br /><br>5. Change in 6MWT distance at EOT in the LAI arm compared to a multi drug<br /><br>regimen alone<br /><br>6. Change from Baseline (Day 1) at Month 6 in the SGRQ.</p><br>