Clinical Trials List
Protocol NumberINS-212
NCT Number(ClinicalTrials.gov Identfier)NCT02344004
2015-10-01 - 2018-09-30
Phase III
Terminated5
ICD-10A31.0
Pulmonary mycobacterial infection
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
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Trial Applicant
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Sponsor
Insmed Incorporated
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 周建宏 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chung-Yu Chen 未分科
- JANN-YUAN WANG Division of Thoracic Medicine
- 樹金忠 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Nontuberculous Mycobacterial (NTM) Lung Infections caused by Mycobacterium avium complex (MAC)
Objectives
Primary Objective
1. To evaluate the efficacy of LAI (590 mg) administered once daily (QD),
when added to a multi-drug regimen, for achieving culture conversion (3
consecutive negative sputum cultures) by Month 6 compared to a multi-drug
regimen alone
Secondary Objectives
1. To evaluate the efficacy of LAI (590 mg) administered QD when added to a
multi-drug regimen on the six-minute walk test (6MWT) at Month 6
compared to a multi-drug regimen alone
2. To evaluate the efficacy of LAI (590 mg) QD when added to a multi-drug
regimen on the durability of treatment success 3 months after the end of total
treatment course (negative sputum culture after 3 months off-treatment)
3. To evaluate the efficacy of LAI (590 mg) administered QD when added to a
multi-drug regimen for time to culture conversion compared to a multi-drug
regimen alone
4. To evaluate the efficacy of LAI (590 mg) administered QD, when added to a
multi-drug regimen, for achieving sustainability (consecutive negative
sputum cultures [with no more than 2 consecutive broth positive cultures] for
12 months on treatment) compared to a multi-drug regimen alone
5. To evaluate the efficacy of LAI (590 mg) administered QD when added to a
multi-drug regimen on the 6MWT at End of Therapy (EOT) compared to a
multi-drug regimen alone
6. To evaluate patient-reported symptoms of NTM and change from Baseline
(Day 1) in quality of life scores on the St. George’s Respiratory
Questionnaire (SGRQ) at Month 6
Test Drug
Liposomal Amikacin for Inhalation(LAI)
Active Ingredient
Amikacin sulfate
Dosage Form
inhalation dosage forms
Dosage
590mg
Endpoints
PRIMARY EFFICACY ENDPOINT
The primary endpoint is the proportion of subjects achieving culture conversion
(3 consecutive negative sputum cultures collected monthly without relapse or
recurrence) by Month 6 in the LAI arm compared to multi-drug regimen alone.
SECONDARY EFFICACY ENDPOINTS
1. Change in 6MWT distance at Month 6 in the LAI arm compared to a
multi-drug regimen alone
2. Proportion of subjects achieving culture conversion with durability after
3 months off treatment in the LAI arm compared to a multi-drug regimen
alone in all evaluable subjects
3. Time to culture conversion in the LAI arm compared to a multi-drug
regimen alone at Month 6
4. Proportion of subjects achieving culture conversion with sustainability at
the EOT in the LAI arm compared to a multi-drug regimen alone
5. Change in 6MWT distance at EOT in the LAI arm compared to a
multi-drug regimen alone
6. Change from Baseline (Day 1) at Month 6 in the SGRQ.
EXPLORATORY ENDPOINTS
1. Change in 6MWT distance at Month 6 for converters versus nonconverters in LAI arm
2. Change in 6MWT distance at Month 6 for converters versus nonconverters for all subjects
3. Change in 6MWT distance at Month 6 for converters versus nonconverters in the multi-drug regimen alone arm
4. Change in BMI at Month 6 in LAI arm compared to a multi-drug
regimen alone
5. Change in 6MWT distance at Month 8 and 3 months off-treatment in the
LAI arm compared to a multi-drug regimen alone
6. Proportion of subjects achieving culture conversion with durability after
12 months off treatment (EOS) in the LAI arm compared to a multi-drug
regimen alone in all evaluable subjects
7. Change from Baseline (Day 1) at Month 6 in the SGRQ –
Part 2 (Activities of Daily Livings)
8. Change from Baseline (Day 1) at EOT in the EQ-5D
9. Proportion of subjects who develop a new strain of MAC in the LAI arm
compared to multi-drug regimen alone
10. Radiological changes in chest CT Scan at EOT in the LAI arm compared
to multi-drug regimen alone, in a sub-set of subjects
11. Mortality at EOS.
The primary endpoint is the proportion of subjects achieving culture conversion
(3 consecutive negative sputum cultures collected monthly without relapse or
recurrence) by Month 6 in the LAI arm compared to multi-drug regimen alone.
SECONDARY EFFICACY ENDPOINTS
1. Change in 6MWT distance at Month 6 in the LAI arm compared to a
multi-drug regimen alone
2. Proportion of subjects achieving culture conversion with durability after
3 months off treatment in the LAI arm compared to a multi-drug regimen
alone in all evaluable subjects
3. Time to culture conversion in the LAI arm compared to a multi-drug
regimen alone at Month 6
4. Proportion of subjects achieving culture conversion with sustainability at
the EOT in the LAI arm compared to a multi-drug regimen alone
5. Change in 6MWT distance at EOT in the LAI arm compared to a
multi-drug regimen alone
6. Change from Baseline (Day 1) at Month 6 in the SGRQ.
EXPLORATORY ENDPOINTS
1. Change in 6MWT distance at Month 6 for converters versus nonconverters in LAI arm
2. Change in 6MWT distance at Month 6 for converters versus nonconverters for all subjects
3. Change in 6MWT distance at Month 6 for converters versus nonconverters in the multi-drug regimen alone arm
4. Change in BMI at Month 6 in LAI arm compared to a multi-drug
regimen alone
5. Change in 6MWT distance at Month 8 and 3 months off-treatment in the
LAI arm compared to a multi-drug regimen alone
6. Proportion of subjects achieving culture conversion with durability after
12 months off treatment (EOS) in the LAI arm compared to a multi-drug
regimen alone in all evaluable subjects
7. Change from Baseline (Day 1) at Month 6 in the SGRQ –
Part 2 (Activities of Daily Livings)
8. Change from Baseline (Day 1) at EOT in the EQ-5D
9. Proportion of subjects who develop a new strain of MAC in the LAI arm
compared to multi-drug regimen alone
10. Radiological changes in chest CT Scan at EOT in the LAI arm compared
to multi-drug regimen alone, in a sub-set of subjects
11. Mortality at EOS.
Inclution Criteria
INCLUSION CRITERIA
To be eligible for enrollment, a prospective patient must meet all of the following criteria:
1. be male or female, 18 years or older
2. continues to be positive for MAC on sputum culture while adhering to a multi-drug
treatment regimen for a minimum duration of 6 months (has not met the protocol
definition of converter while being treated) 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 underlying lung disease
such as nodular bronchiectasis and/or fibrocavitary disease by chest radiography or highresolution chest computed tomography (HRCT)
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 approximately 3 mL of sputum or be willing to undergo an induction
that produces approximately 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.
To be eligible for enrollment, a prospective patient must meet all of the following criteria:
1. be male or female, 18 years or older
2. continues to be positive for MAC on sputum culture while adhering to a multi-drug
treatment regimen for a minimum duration of 6 months (has not met the protocol
definition of converter while being treated) 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 underlying lung disease
such as nodular bronchiectasis and/or fibrocavitary disease by chest radiography or highresolution chest computed tomography (HRCT)
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 approximately 3 mL of sputum or be willing to undergo an induction
that produces approximately 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.
Exclusion Criteria
EXCLUSION CRITERIA
A prospective 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 ≥64)
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, 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,
gentamicin, or streptomycin) within 28 days before Day 1
14. 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/μL 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. Patients receiving continuous oxygen therapy at Screening
23. Patients with disseminated MAC infection
A prospective 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 ≥64)
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, 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,
gentamicin, or streptomycin) within 28 days before Day 1
14. 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/μL 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. Patients receiving continuous oxygen therapy at Screening
23. Patients with disseminated MAC infection
The Estimated Number of Participants
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Taiwan
20 participants
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Global
351 participants
