Study to Evaluate ALIS (Amikacin Liposome Inhalation Suspension) in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex
- Conditions
- Mycobacterium Infections, Nontuberculous
- Interventions
- Registration Number
- NCT04677569
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
The main objective of this study is to evaluate the efficacy of ALIS (amikacin liposome inhalation suspension) + background regimen (azithromycin \[AZI\] + ethambutol \[ETH\]) compared to the ELC (empty liposome control) + background regimen on participant-reported respiratory symptoms at Month 13.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 425
-
Male or female, ≥ 18 years of age (19 years or older in South Korea, 20 years or older in Japan).
-
Current diagnosis of MAC lung infection. MAC or mixed infection with MAC as the dominant species is allowed, with MAC as the intended organism for treatment.
-
A chest computerized tomography (CT) scan, read locally, within 6 months prior to Screening to determine presence and size of pulmonary cavities. Participants 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.
-
Willingness and ability to adhere to prescribed study treatment during the study.
-
Women of childbearing potential (WOCBP) (ie, fertile following menarche and until becoming postmenopausal unless permanently sterile) and fertile men (ie, all men after puberty unless permanently sterile by bilateral orchidectomy) agree to practice a highly effective method of birth control from Day 1 to at least 90 days after the last dose. Examples of such birth controls are:
- true abstinence (refraining from heterosexual intercourse during the entire study),
- copper intrauterine device (IUD),
- hormonal methods (levonorgestrel-releasing intrauterine system, progestogen implant, combined oral contraceptive pill [combined with barrier method]),
- exclusive homosexual relationship, or
- sole male partner who has undergone surgical sterilization with confirmation of azoospermia at least 3 months post procedure.
-
Provide signed informed consent prior to administration of study drugs or performing any study-related procedure.
-
Be able to comply with study drugs use, study visits, and study procedures as defined by the protocol.
-
Men with partners who are WOCBP (pregnant or non-pregnant) agree to use condoms and non-pregnant partners should practice a highly effective method of birth control
- Diagnosis of cystic fibrosis (CF).
- History of more than 3 MAC lung infections (a 4th MAC lung infection is not eligible)
- Received any mycobacterial antibiotic treatment for current MAC lung infection
- 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
- Relapse of prior MAC lung infection, defined as positive sputum culture for MAC ≤6 months of cessation of prior successful treatment
- Evidence of any pulmonary cavity ≥ 2 cm in diameter, as determined by chest CT scan, read locally, during Screening or within 6 months prior to Screening
- Radiographic finding of new lobar consolidation, atelectasis, significant pleural effusion, or pneumothorax during routine clinical care within 2 months prior to Screening
- 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
- Acute pulmonary exacerbation (eg, chronic obstructive pulmonary disease (COPD) or bronchiectasis) requiring treatment with antibiotics, or corticosteroids (intravenous [IV] or oral), within 4 weeks prior to and during Screening
- Current smoker
- History of lung transplantation
- Prior exposure to ALIS (including clinical study)
- Known hypersensitivity or contraindications to use to ALIS, aminoglycosides, or any of their excipients
- Disseminated MAC infection
- Administration of any investigational drug within 8 weeks prior to Screening
- Known or suspected acquired immunodeficiency syndromes (Human Immunodeficiency Virus (HIV) -positive, regardless of CD4 counts). Other immunodeficiency syndromes that may interfere with study participation in the opinion of the Investigator
- Current alcohol, medication, or illicit drug abuse
- Known and active COVID-19 infection
- Known hypersensitivity or contraindications to use of ethambutol, azithromycin (including other macrolides or ketolides), or any of their excipients per local labeling guidance.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ALIS + Background Regimen ALIS Participants will be administered 590 mg of ALIS (amikacin liposome inhalation suspension) once daily. Participants will also be administered azithromycin 250 mg and ethambutol 15 mg/kg, once daily. ALIS + Background Regimen Azithromycin Participants will be administered 590 mg of ALIS (amikacin liposome inhalation suspension) once daily. Participants will also be administered azithromycin 250 mg and ethambutol 15 mg/kg, once daily. ALIS + Background Regimen Ethambutol Participants will be administered 590 mg of ALIS (amikacin liposome inhalation suspension) once daily. Participants will also be administered azithromycin 250 mg and ethambutol 15 mg/kg, once daily. ELC + Background Regimen Azithromycin Participants will be administered ELC (empty liposome control), a visually matching placebo to ALIS (amikacin liposome inhalation suspension), once daily. Participants will also be administered azithromycin 250 mg and ETH (ethambutol) 15 mg/kg, once daily. ELC + Background Regimen ELC (matching placebo for ALIS) Participants will be administered ELC (empty liposome control), a visually matching placebo to ALIS (amikacin liposome inhalation suspension), once daily. Participants will also be administered azithromycin 250 mg and ETH (ethambutol) 15 mg/kg, once daily. ELC + Background Regimen Ethambutol Participants will be administered ELC (empty liposome control), a visually matching placebo to ALIS (amikacin liposome inhalation suspension), once daily. Participants will also be administered azithromycin 250 mg and ETH (ethambutol) 15 mg/kg, once daily.
- Primary Outcome Measures
Name Time Method Change from Baseline in Respiratory Symptom Score at Month 13 Baseline to Month 13
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Durable Culture Conversion at Month 15 Month 15 Change from Baseline in Fatigue Symptom Score at Month 13 Baseline to Month 13 Percentage of Participants Achieving Culture Conversion by Month 6 Month 6 Percentage of Participants Achieving Culture Conversion by Month 12 Month 12 Percentage of Participants Achieving Culture Conversion by Month 13 Month 13 Percentage of Participants Achieving Culture Conversion During Treatment Baseline to Month 12 Time to Culture Conversion Baseline to Month 12 Time to the First Negative Culture Baseline to Month 12 Percentage of Participants Who Develop a Mycobacterium avium Complex (MAC) Isolate with Amikacin Minimum Inhibitory Concentration (MIC) ≥ 128 μg/mL More Than One Time Baseline to Month 15 Percentage of Participants Achieving Culture Conversion and a Subsequent at Least one MAC Positive Culture in Agar Media or Broth Media in at Least 2 Consecutive Visits With Matching Species and Genome at Screening/ Baseline Baseline to Month 15 Percentage of Participants Achieving Culture Conversion and a Subsequently have at least One MAC Positive Culture in Agar Media or Broth Media in at Least 2 Consecutive Visits With Differing Species and/or Genome at Screening/ Baseline Baseline to Month 15 Percentage of Participants Meeting the Within-subject Meaningful Change Threshold as Reflected in the Change in Respiratory Symptom Scores Computed From Baseline to Month 13 Baseline to Month 13 Number of Participants Who Experience an Adverse Event (AEs) Baseline to Month 15
Trial Locations
- Locations (162)
USA014
🇺🇸Saint Petersburg, Florida, United States
USA084
🇺🇸Sebastian, Florida, United States
USA067
🇺🇸Tampa, Florida, United States
USA066
🇺🇸Augusta, Georgia, United States
USA029
🇺🇸Rincon, Georgia, United States
USA079
🇺🇸Coeur d'Alene, Idaho, United States
USA031
🇺🇸Chicago, Illinois, United States
USA037
🇺🇸Kansas City, Kansas, United States
USA002
🇺🇸New Orleans, Louisiana, United States
USA099
🇺🇸Lexington, Massachusetts, United States
USA077
🇺🇸Springfield, Massachusetts, United States
USA013
🇺🇸Rochester, Minnesota, United States
USA061
🇺🇸Saint Louis, Missouri, United States
USA009
🇺🇸Omaha, Nebraska, United States
USA069
🇺🇸Hillsborough, New Jersey, United States
USA065
🇺🇸Bayside, New York, United States
USA059
🇺🇸Bronx, New York, United States
USA011
🇺🇸New York, New York, United States
USA064
🇺🇸Cincinnati, Ohio, United States
USA040
🇺🇸Philadelphia, Pennsylvania, United States
USA092
🇺🇸Providence, Rhode Island, United States
USA044
🇺🇸Anderson, South Carolina, United States
USA024
🇺🇸Charleston, South Carolina, United States
USA020
🇺🇸Charleston, South Carolina, United States
USA022
🇺🇸Franklin, Tennessee, United States
USA078
🇺🇸Nashville, Tennessee, United States
USA091
🇺🇸Denison, Texas, United States
USA006
🇺🇸San Antonio, Texas, United States
USA052
🇺🇸Tyler, Texas, United States
USA083
🇺🇸Charlottesville, Virginia, United States
ARG007
🇦🇷San Miguel de Tucumán, Tucumán, Argentina
AUS006
🇦🇺Concord, New South Wales, Australia
AUS012
🇦🇺Birtinya, Queensland, Australia
AUS010
🇦🇺Chermside, Queensland, Australia
AUS013
🇦🇺Douglas, Queensland, Australia
AUS003
🇦🇺Greenslopes, Queensland, Australia
AUS016
🇦🇺Herston, Queensland, Australia
AUS014
🇦🇺Meadowbrook, Queensland, Australia
AUS011
🇦🇺Woolloongabba, Queensland, Australia
AUS008
🇦🇺Adelaide, South Australia, Australia
AUS007
🇦🇺Clayton, Victoria, Australia
AUS005
🇦🇺Perth, Australia
AUT001
🇦🇹Linz, Oberösterreich, Austria
BEL003
🇧🇪Bruxelles, Brussels, Belgium
BEL002
🇧🇪Ghent, Belgium
BEL001
🇧🇪Leuven, Belgium
CAN003
🇨🇦Winnepeg, Manitoba, Canada
CAN002
🇨🇦Toronto, Ontario, Canada
CAN004
🇨🇦Windsor, Ontario, Canada
CHL001
🇨🇱Curico, Maule, Chile
CHL003
🇨🇱Valparaíso, Chile
DNK005
🇩🇰Vejle, South Denmark, Denmark
DNK004
🇩🇰Aalborg, Denmark
DNK003
🇩🇰Odensa C, Denmark
FRA016
🇫🇷Strasbourg, Bas-Rhin, France
FRA015
🇫🇷Pessac, Gironde, France
FRA008
🇫🇷Nantes, Loire-Atlantique, France
FRA006
🇫🇷Amiens cedex 1, France
FRA001
🇫🇷Marseille, France
FRA009
🇫🇷Paris, France
FRA013
🇫🇷Paris, France
FRA004
🇫🇷Saint Denis Cedex, France
FRA003
🇫🇷Saint Pierre, France
GER013
🇩🇪Gauting, Bayern, Germany
GER005
🇩🇪München, Bayern, Germany
GER014
🇩🇪Köln, Nordrhein-Westfalen, Germany
GER011
🇩🇪Köln, Nordrhein-Westfalen, Germany
GER008
🇩🇪Berlin, Germany
GER009
🇩🇪Essen, Germany
GER007
🇩🇪Hannover, Germany
GRC002
🇬🇷Athens, Attiki, Greece
HUN002
🇭🇺Budapest, Hungary
ISR008
🇮🇱Tel Aviv-Yafo, Tel-Aviv, Israel
ISR001
🇮🇱Ashkelon, Israel
ISR007
🇮🇱Haifa, Israel
ISR005
🇮🇱Jerusalem, Israel
ISR003
🇮🇱Petah Tikva, Israel
ISR004
🇮🇱Ramat Gan, Israel
ITA006
🇮🇹Modena, Emilia-Romagna, Italy
ITA011
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
ITA010
🇮🇹Genova, Liguria, Italy
ITA004
🇮🇹Firenze, Italy
ITA001
🇮🇹Milano, Italy
ITA007
🇮🇹Monza, Italy
ITA003
🇮🇹Pavia, Italy
ITA005
🇮🇹Roma, Italy
JPN011
🇯🇵Nagoya-shi, Aiti, Japan
JPN020
🇯🇵Kita Kyushu-shi, Hukuoka, Japan
JPN022
🇯🇵Yokohama-Shi Tsuzuki-Ku, Kanagawa, Japan
JPN017
🇯🇵Matsusaka-Shi, Mie, Japan
JPN018
🇯🇵Nagasaki-Shi, Nagasaki, Japan
JPN023
🇯🇵Kurashiki-Shi, Okayama, Japan
JPN019
🇯🇵Izumo-Shi, Simane, Japan
JPN014
🇯🇵Hamamatsu-shi, Sizuoka, Japan
JPN008
🇯🇵Shinjuku-ku, Tokyo, Japan
JPN001
🇯🇵Fukui, Japan
JPN004
🇯🇵Fukuoka, Japan
JPN003
🇯🇵Jonan-ku, Japan
JPN010
🇯🇵Kiyose, Japan
JPN006
🇯🇵Nagano, Japan
JPN012
🇯🇵Naka-gun, Japan
JPN002
🇯🇵Sakai-shi, Japan
JPN009
🇯🇵Shimonoseki, Japan
JPN005
🇯🇵Tokyo, Japan
JPN016
🇯🇵Toyonaka-Shi, Ôsaka, Japan
KOR005
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
KOR007
🇰🇷Seongbuk-Gu, Seoul Teugbyeolsi, Korea, Republic of
KOR006
🇰🇷Incheon, Korea, Republic of
KOR004
🇰🇷Seoul, Korea, Republic of
KOR002
🇰🇷Seoul, Korea, Republic of
KOR009
🇰🇷Seoul, Korea, Republic of
KOR003
🇰🇷Seoul, Korea, Republic of
KOR001
🇰🇷Seoul, Korea, Republic of
NZL003
🇳🇿Hastings, Hawkes's Bay, New Zealand
NZL002
🇳🇿Hamilton, Waikato, New Zealand
NZL001
🇳🇿Christchurch, New Zealand
POL003
🇵🇱Kielce, Swietokrzyskie, Poland
PRT002
🇵🇹Braga, Portugal
PRT003
🇵🇹Lisboa, Portugal
ESP009
🇪🇸L'hospitalet De Llobregat, Barcelona, Spain
ESP007
🇪🇸Vigo, Pontevedra, Spain
ESP002
🇪🇸Barcelona, Spain
ESP003
🇪🇸Barcelona, Spain
ESP005
🇪🇸Girona, Spain
ESP010
🇪🇸Madrid, Spain
ESP001
🇪🇸Madrid, Spain
ESP011
🇪🇸Pamplona, Spain
ESP006
🇪🇸Pontevedra, Spain
ESP012
🇪🇸Sevilla, Spain
TWN004
🇨🇳Chiayi, Taiwan
TWN001
🇨🇳Douliu, Taiwan
TWN012
🇨🇳Hsinchu City, Taiwan
TWN005
🇨🇳Kaohsiung, Taiwan
TWN003
🇨🇳Kaohsiung, Taiwan
TWN007
🇨🇳New Taipei City, Taiwan
TWN011
🇨🇳Taipei City, Taiwan
TWN010
🇨🇳Taipei, Taiwan
TWN008
🇨🇳Taipei, Taiwan
TUR003
🇹🇷Izmir, Turkey
TUR002
🇹🇷Kocaeli, Turkey
GBR009
🇬🇧Plymouth, Devon, United Kingdom
GBR008
🇬🇧Birmingham, West Midlands, United Kingdom
GBR005
🇬🇧Aberdeen, United Kingdom
GBR001
🇬🇧Cambridge, United Kingdom
GBR002
🇬🇧Dundee, United Kingdom
GBR007
🇬🇧London, United Kingdom
GBR010
🇬🇧London, United Kingdom
GBR003
🇬🇧London, United Kingdom
USA047
🇺🇸Jacksonville, Florida, United States
USA042
🇺🇸Kissimmee, Florida, United States
USA096
🇺🇸Naples, Florida, United States
USA089
🇺🇸Temple, Texas, United States
CHL002
🇨🇱Quillota, Chile
USA062
🇺🇸Fresno, California, United States
USA090
🇺🇸Newport Beach, California, United States
USA058
🇺🇸Sacramento, California, United States
USA048
🇺🇸San Diego, California, United States
USA081
🇺🇸San Francisco, California, United States
USA050
🇺🇸Stanford, California, United States
USA023
🇺🇸Washington, District of Columbia, United States
USA080
🇺🇸Bradenton, Florida, United States
USA003
🇺🇸Clearwater, Florida, United States