Study to Evaluate ALIS (Amikacin Liposome Inhalation Suspension) in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex (ENCORE)

ENCORE - A Randomized, Double-Blind, Placebo-Controlled, Active Comparator, Multicenter Study to Evaluate the Efficacy and Safety of an Amikacin Liposome Inhalation Suspension (ALIS)-Based Regimen in Adult Subjects With Newly Diagnosed Nontuberculous Mycobacterial (NTM) Lung Infection Caused by Mycobacterium Avium Complex (MAC)

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.

Study Overview

• Status: Completed
• Conditions: Mycobacterium Infections, Nontuberculous
• Intervention / Treatment: Drug: ALIS; Drug: Azithromycin; Drug: Ethambutol; Drug: ELC (matching placebo for ALIS)

• Study Type: Interventional
• Enrollment (Actual): 425
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad autAnoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • ARG004
    • Quilmes, Buenos Aires, Argentina, B1878FNR
      • ARG005
    • Villa Vatteone, Buenos Aires, Argentina, B1853AIK
      • ARG006
  • CArdoba
    • CArdoba, CArdoba, Argentina, X5003DCE
      • ARG003
    • Córdoba, CArdoba, Argentina, 5000
      • ARG002
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DTC
      • ARG001
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • ARG007
• Australia
  • Perth, Australia, 5000
    • AUS005
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • AUS006
    • New Lambton Heights, New South Wales, Australia, 2305
      • AUS004
    • Westmead, New South Wales, Australia, 2145
      • AUS002
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • AUS012
    • Chermside, Queensland, Australia, 4032
      • AUS010
    • Douglas, Queensland, Australia, 4814
      • AUS013
    • Greenslopes, Queensland, Australia, 4120
      • AUS003
    • Herston, Queensland, Australia, 4029
      • AUS016
    • Meadowbrook, Queensland, Australia, 4131
      • AUS014
    • South Brisbane, Queensland, Australia, 4101
      • AUS001
    • Woolloongabba, Queensland, Australia, 4102
      • AUS011
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • AUS008
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • AUS007
    • Melbourne, Victoria, Australia, 3001
      • AUS009
  • Western Australia
    • Spearwood, Western Australia, Australia, 6163
      • AUS015
• Austria
  • OberAsterreich
    • Wels, OberAsterreich, Austria, 4600
      • AUT003
  • Upper Austria
    • Linz, Upper Austria, Austria, 4040
      • AUT001
• Belgium
  • Ghent, Belgium, 9000
    • BEL002
  • Leuven, Belgium, 3000
    • BEL001
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1000
      • BEL003
• Canada
  • Manitoba
    • Winnepeg, Manitoba, Canada, R2H 2A6
      • CAN003
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • CAN002
    • Windsor, Ontario, Canada, N8X-5A6
      • CAN004
• Chile
  • Quillota, Chile, 2260000
    • CHL002
  • Talca, Chile
    • CHL004
  • Valparaíso, Chile, 2340000
    • CHL003
  • Maule Region
    • Curicó, Maule Region, Chile, 3440000
      • CHL001
• Denmark
  • Aalborg, Denmark, 9000
    • DNK004
  • Aarhus N, Denmark, 8200
    • DNK002
  • Odensa C, Denmark, 5000
    • DNK003
  • Region Syddanmark
    • Vejle, Region Syddanmark, Denmark, 7100
      • DNK005
  • Zeeland
    • Roskilde, Zeeland, Denmark, 4000
      • DNK001
• France
  • Amiens, France, 80054
    • FRA006
  • Brest, France, 29609
    • FRA005
  • Caen, France, 14033
    • FRA007
  • Créteil, France, 94000
    • FRA002
  • Marseille, France, 13285
    • FRA001
  • Paris, France, 75018
    • FRA009
  • Paris, France, 75020
    • FRA013
  • Paris, France, 75013
    • FRA014
  • Saint-Denis, France, 97405
    • FRA004
  • Saint-Pierre, France, 97448
    • FRA003
  • Toulouse, France, 31400
    • FRA011
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 6000
      • FRA012
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67091
      • FRA016
  • Gironde
    • Pessac, Gironde, France, 33064
      • FRA015
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • FRA010
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • FRA008
• Germany
  • Berlin, Germany, 13125
    • GER008
  • Dresden, Germany, 1307
    • GER006
  • Essen, Germany, 45127
    • GER009
  • Frankfurt, Germany, 69590
    • GER002
  • Freiburg im Breisgau, Germany, 79106
    • GER004
  • Hanover, Germany, 30625
    • GER007
  • Bavaria
    • Donaustauf, Bavaria, Germany, 93093
      • GER001
    • Gauting, Bavaria, Germany, 82131
      • GER013
    • München, Bavaria, Germany, 80335
      • GER005
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14467
      • GER012
  • Hesse
    • Immenhausen, Hesse, Germany, 34376
      • GER010
  • Lower Saxony
    • Borstel, Lower Saxony, Germany, 23845
      • GER003
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50678
      • GER014
    • Cologne, North Rhine-Westphalia, Germany, 51109
      • GER011
• Greece
  • Alexandroupoli, Greece, 681 00
    • GRC003
  • Heraklion, Greece, 71110
    • GRC001
  • Attica
    • Athens, Attica, Greece, 11527
      • GRC002
• Hungary
  • Budapest, Hungary, 1121
    • HUN002
  • Törökbálint, Hungary, 2045
    • HUN001
• Israel
  • Ashkelon, Israel, 78100
    • ISR001
  • Beer-Yaakov, Israel, 70300
    • ISR002
  • Haifa, Israel, 34362
    • ISR007
  • Jerusalem, Israel, 91120
    • ISR005
  • Petah Tikva, Israel, 4910000
    • ISR003
  • Ramat Gan, Israel, 52621
    • ISR004
  • Tel Aviv
    • Tel Aviv, Tel Aviv, Israel, 64239
      • ISR008
• Italy
  • Florence, Italy, 50134
    • ITA004
  • Milan, Italy, 20122
    • ITA001
  • Milan, Italy, 20123
    • ITA009
  • Monza, Italy, 20900
    • ITA007
  • Pavia, Italy, 27100
    • ITA003
  • Roma, Italy, 00168
    • ITA005
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41124
      • ITA006
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • ITA011
  • Liguria
    • Genoa, Liguria, Italy, 16128
      • ITA010
  • Milano
    • Milan, Milano, Italy, 20162
      • ITA002
  • Tuscany
    • Siena, Tuscany, Italy, 53100
      • ITA008
• Japan
  • Fukui, Japan, 910-8526
    • JPN001
  • Fukuoka, Japan, 819-8555
    • JPN004
  • Jonan-ku, Japan
    • JPN003
  • Kiyose, Japan, 204-8522
    • JPN010
  • Nagano, Japan, 380-0928
    • JPN006
  • Naka-gun, Japan, 319-1113
    • JPN012
  • Sakaishi, Japan, 591-8555
    • JPN002
  • Shimonoseki, Japan, 750-8520
    • JPN009
  • Tokyo, Japan
    • JPN005
  • Aiti
    • Nagoya, Aiti, Japan, 465-0065
      • JPN011
  • Hukuoka
    • Kita Kyushu-shi, Hukuoka, Japan, 807-8556
      • JPN020
  • Kanagawa
    • Yokohama-Shi Tsuzuki-Ku, Kanagawa, Japan, 224-0032
      • JPN022
  • Mie-ken
    • Matsusaka-Shi, Mie-ken, Japan, 515-0073
      • JPN017
  • Nagasaki
    • Nagasaki, Nagasaki, Japan, 852-8501
      • JPN018
  • Okayama-ken
    • Kurashiki-Shi, Okayama-ken, Japan, 710-0052
      • JPN023
  • Shimane
    • Izumo-Shi, Shimane, Japan, 693-0021
      • JPN019
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 434-8511
      • JPN014
  • Tokyo
    • Kiyose-Shi, Tokyo, Japan, 204-0023
      • JPN015
    • Shinjuku-ku, Tokyo, Japan, 1628655
      • JPN008
    • Ōta-ku, Tokyo, Japan, 143-8541
      • JPN021
  • Ôsaka
    • Toyonaka-Shi, Ôsaka, Japan, 560-0045
      • JPN016
• New Zealand
  • Auckland, New Zealand, 1051
    • NZL004
  • Christchurch, New Zealand, 8461
    • NZL001
  • Hawkes's Bay
    • Hastings, Hawkes's Bay, New Zealand, 4122
      • NZL003
  • Waikato Region
    • Hamilton, Waikato Region, New Zealand, 3204
      • NZL002
• Poland
  • Świętokrzyskie Voivodeship
    • Kielce, Świętokrzyskie Voivodeship, Poland, 25-751
      • POL003
• Portugal
  • Braga, Portugal, 4710-243
    • PRT002
  • Lisbon, Portugal, 1796-001
    • PRT003
• South Korea
  • Incheon, South Korea, 22332
    • KOR006
  • Seoul, South Korea, 03722
    • KOR004
  • Seoul, South Korea, 05505
    • KOR002
  • Seoul, South Korea, 06591
    • KOR009
  • Seoul, South Korea, 06973
    • KOR003
  • Seoul, South Korea
    • KOR001
  • Gyeonggido
    • Ansan-si, Gyeonggido, South Korea, 15355
      • KOR008
    • Seongnam-si, Gyeonggido, South Korea, 13620
      • KOR005
  • Seoul Teugbyeolsi
    • Seongbuk-Gu, Seoul Teugbyeolsi, South Korea, 02841
      • KOR007
• Spain
  • Barcelona, Spain, 08003
    • ESP002
  • Barcelona, Spain, 8035
    • ESP003
  • Barcelona, Spain, 8025
    • ESP008
  • Girona, Spain, 17007
    • ESP005
  • Madrid, Spain, 28034
    • ESP001
  • Madrid, Spain, 28046
    • ESP004
  • Madrid, Spain, 28007
    • ESP010
  • Pamplona, Spain, 31008
    • ESP011
  • Pontevedra, Spain, 36001
    • ESP006
  • Seville, Spain, 41013
    • ESP012
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • ESP009
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • ESP007
• Taiwan
  • Douliu, Taiwan, 640
    • TWN001
  • Hsinchu, Taiwan, 300
    • TWN012
  • Kaohsiung City, Taiwan, 807
    • TWN005
  • Kaohsiung City, Taiwan, 813
    • TWN003
  • New Taipei City, Taiwan, 23561
    • TWN007
  • Taipei, Taiwan, 110
    • TWN010
  • Taipei, Taiwan, 11217
    • TWN008
  • Taipei, Taiwan, 10002
    • TWN006
  • Taipei, Taiwan, 11490
    • TWN009
  • Taipei, Taiwan, 10002
    • TWN011
  • Taipei, Taiwan, 116
    • TWN002
  • Chiayi
    • Chiayi City, Chiayi, Taiwan, 613
      • TWN004
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35110
    • TUR003
  • Kocaeli, Turkey (Türkiye), 41380
    • TUR002
  • Istanbul
    • Maltepe, Istanbul, Turkey (Türkiye), 34844
      • TUR004
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • GBR005
  • Cambridge, United Kingdom, CB2 OAY
    • GBR001
  • Dundee, United Kingdom, DD1 9SY
    • GBR002
  • Liverpool, United Kingdom, L14 3PE
    • GBR004
  • London, United Kingdom, EC1A 7BE
    • GBR007
  • London, United Kingdom, NW32QG
    • GBR010
  • London, United Kingdom, SW3 6NP
    • GBR003
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8BQ
      • GBR009
  • Lancashire
    • Salford, Lancashire, United Kingdom, M6 8HD
      • GBR012
  • West Glamorgan
    • Swansea, West Glamorgan, United Kingdom, SA6 6NL
      • GBR013
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • GBR008
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1711
      • USA008
  • California
    • Fresno, California, United States, 93701
      • USA062
    • Los Angeles, California, United States, 90033-5313
      • USA060
    • Newport Beach, California, United States, 92663
      • USA090
    • Sacramento, California, United States, 95817
      • USA058
    • San Diego, California, United States, 92103
      • USA048
    • San Francisco, California, United States, 94143
      • USA081
    • Santa Barbara, California, United States, 93105
      • USA055
    • Stanford, California, United States, 94305
      • USA050
  • Colorado
    • Denver, Colorado, United States, 80206
      • USA001
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • USA023
  • Florida
    • Bradenton, Florida, United States, 34209
      • USA080
    • Brandon, Florida, United States, 33511-5719
      • USA028
    • Clearwater, Florida, United States, 33765
      • USA003
    • Jacksonville, Florida, United States, 32204
      • USA043
    • Jacksonville, Florida, United States, 32224
      • USA047
    • Jacksonville, Florida, United States, 32207-8567
      • USA072
    • Jacksonville, Florida, United States, 32209-6511
      • USA085
    • Kissimmee, Florida, United States, 34746
      • USA042
    • Leesburg, Florida, United States, 34748
      • USA019
    • Naples, Florida, United States, 34102-5444
      • USA039
    • Naples, Florida, United States, 34102
      • USA096
    • Naples, Florida, United States, 34102
      • USA097
    • New Port Richey, Florida, United States, 34652
      • USA046
    • Sarasota, Florida, United States, 34239-2913
      • USA054
    • Sebastian, Florida, United States, 32958
      • USA084
    • Sebring, Florida, United States, 33870
      • USA026
    • St. Petersburg, Florida, United States, 33704-2733
      • USA070
    • St. Petersburg, Florida, United States, 33707
      • USA014
    • Tampa, Florida, United States, 33606
      • USA067
    • Tampa, Florida, United States, 33614-7101
      • USA068
    • Weston, Florida, United States, 33331
      • USA053
  • Georgia
    • Atlanta, Georgia, United States, 30342-2147
      • USA038
    • Augusta, Georgia, United States, 30912
      • USA066
    • Lawrenceville, Georgia, United States, 30046-3325
      • USA004
    • Rincon, Georgia, United States, 31326
      • USA029
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • USA079
  • Illinois
    • Chicago, Illinois, United States, 60611
      • USA031
    • Springfield, Illinois, United States, 62702-4968
      • USA073
    • Springfield, Illinois, United States, 62702
      • USA030
  • Iowa
    • Iowa City, Iowa, United States, 52242-1081
      • USA074
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • USA037
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • USA002
  • Maryland
    • Baltimore, Maryland, United States, 21224-3057
      • USA017
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
      • USA099
    • Springfield, Massachusetts, United States, 01107
      • USA077
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • USA013
  • Missouri
    • Columbia, Missouri, United States, 65212-1000
      • USA082
    • St Louis, Missouri, United States, 63110
      • USA061
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • USA009
    • Omaha, Nebraska, United States, 68124
      • USA045
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • USA069
    • Toms River, New Jersey, United States, 08755-8000
      • USA032
  • New York
    • Bayside, New York, United States, 11361
      • USA065
    • East Syracuse, New York, United States, 13057
      • USA088
    • New York, New York, United States, 10017
      • USA011
    • The Bronx, New York, United States, 10461
      • USA059
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • USA076
    • Charlotte, North Carolina, United States, 28273
      • USA035
    • Charlotte, North Carolina, United States, 28277-8915
      • USA033
    • Durham, North Carolina, United States, 27710-0001
      • USA051
    • Mooresville, North Carolina, United States, 28117
      • USA034
    • Winston-Salem, North Carolina, United States, 27103
      • USA007
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • USA064
    • Cincinnati, Ohio, United States, 45242-4402
      • USA075
    • Cleveland, Ohio, United States, 44195
      • USA018
    • Columbus, Ohio, United States, 43210-1240
      • USA063
  • Oregon
    • Portland, Oregon, United States, 97213-2982
      • USA071
    • Portland, Oregon, United States, 97239
      • USA025
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • USA015
    • Philadelphia, Pennsylvania, United States, 19104
      • USA040
    • Philadelphia, Pennsylvania, United States, 19107
      • USA093
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • USA092
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • USA044
    • Charleston, South Carolina, United States, 29414
      • USA024
    • Charleston, South Carolina, United States, 29425
      • USA020
    • Rock Hill, South Carolina, United States, 29732
      • USA012
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • USA022
    • Hendersonville, Tennessee, United States, 37075
      • USA041
    • Nashville, Tennessee, United States, 37232
      • USA078
  • Texas
    • Dallas, Texas, United States, 75246
      • USA016
    • Dallas, Texas, United States, 75246
      • USA100
    • Denison, Texas, United States, 75020
      • USA091
    • Houston, Texas, United States, 77070-1190
      • USA086
    • McKinney, Texas, United States, 75069-8085
      • USA021
    • San Antonio, Texas, United States, 78258
      • USA006
    • Temple, Texas, United States, 76508
      • USA089
    • Tyler, Texas, United States, 75708
      • USA052
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • USA083
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • USA087

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALIS + Background Regimen; 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.	Drug: ALIS; Inhalation via nebulization over approximately 6 to 15 minutes; Other Names: ARIKAYCE®; Amikacin liposome inhalation suspension; Drug: Azithromycin; Oral tablet; Other Names: Zithromax; AZI; Drug: Ethambutol; Oral tablet; Other Names: ETH; Myambutol
Placebo Comparator: ELC + Background Regimen; 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.	Drug: Azithromycin; Oral tablet; Other Names: Zithromax; AZI; Drug: Ethambutol; Oral tablet; Other Names: ETH; Myambutol; Drug: ELC (matching placebo for ALIS); Inhalation via nebulization over approximately 6 to 15 minutes; Other Names: Empty liposome control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Respiratory Symptom Score at Month 13	Baseline to Month 13

Secondary Outcome Measures

Outcome Measure	Time Frame
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 12	Month 12
Percentage of Participants Achieving Culture Conversion by Month 6	Month 6
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
Number of Participants Who Experience an Adverse Event (AEs)	Baseline to Month 15
Percentage of Participants Achieving Culture Conversion by Month 13	Month 13
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

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): November 21, 2025
• Study Completion (Actual): January 15, 2026

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Nontuberculous Mycobacterial Lung Infection; Mycobacterium avium complex; Arikayce®
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium avium-intracellulare Infection; Organic Chemicals; Amines; Macrolides; Lactones; Erythromycin; Polyketides; Ethylenediamines; Diamines; Polyamines; Azithromycin; Ethambutol
• Other Study ID Numbers: INS-416; 2020-003079-16 (EudraCT Number); 2023-505273-33-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No