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

Sponsor
Insmed Incorporated (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04677569
Collaborator
(none)
250
Enrollment
169
Locations
2
Arms
28.6
Anticipated Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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 Mycobact
Actual Study Start Date :
Apr 1, 2021
Anticipated Primary Completion Date :
Aug 21, 2023
Anticipated Study Completion Date :
Aug 21, 2023

Arms and Interventions

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:
  • Amikacin liposome inhalation suspension
  • ARIKAYCE®

    • Drug: Azithromycin
    Oral tablet
    Other Names:
  • AZI
  • Zithromax

    • 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:
  • AZI
  • Zithromax

    • 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from Baseline in Respiratory Symptom Score at Month 13 [Baseline to Month 13]

    Secondary Outcome Measures

    1. Percentage of Participants Achieving Durable Culture Conversion at Month 15 [Month 15]

    2. Change from Baseline in Fatigue Symptom Score at Month 13 [Baseline to Month 13]

    3. Percentage of Participants Achieving Culture Conversion by Month 12 [Month 12]

    4. Percentage of Participants Achieving Culture Conversion by Month 6 [Month 6]

    5. Percentage of Participants Achieving Culture Conversion During Treatment [Baseline to Month 12]

    6. Time to Culture Conversion [Baseline to Month 12]

    7. Time to the First Negative Culture [Baseline to Month 12]

    8. 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]

    9. 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]

    10. 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]

    11. Percentage of Participants Meeting the Within-subject Meaningful Change Threshold as Reflected in Patient Reported Outcome Changes Scores Computed from Baseline in Participant-reported Symptoms [Baseline to Month 15]

    12. Number of Participants Who Experience an Adverse Event (AEs) [Baseline to Month 15]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    • 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, 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 to ethambutol, azithromycin (including other macrolides or ketolides), or any of their excipients per local labeling guidance.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USA008 Birmingham Alabama United States 35233-1711
    2 USA062 Fresno California United States 93701-2302
    3 USA060 Los Angeles California United States 90033-5320
    4 USA058 Sacramento California United States 95817-2201
    5 USA048 San Diego California United States 92103-1911
    6 USA055 Santa Barbara California United States 93105
    7 USA050 Stanford California United States 94305
    8 USA001 Denver Colorado United States 80206
    9 USA023 Washington District of Columbia United States 20007
    10 USA003 Clearwater Florida United States 33765
    11 USA043 Jacksonville Florida United States 32204
    12 USA072 Jacksonville Florida United States 32207-8202
    13 USA047 Jacksonville Florida United States 32224
    14 USA042 Kissimmee Florida United States 34746
    15 USA019 Leesburg Florida United States 34748
    16 USA039 Naples Florida United States 34102-5444
    17 USA046 New Port Richey Florida United States 34652
    18 USA014 Saint Petersburg Florida United States 33707
    19 USA054 Sarasota Florida United States 34239
    20 USA067 Tampa Florida United States 33606-3603
    21 USA068 Tampa Florida United States 33614
    22 USA053 Weston Florida United States 33331
    23 USA038 Atlanta Georgia United States 30342-2147
    24 USA066 Augusta Georgia United States 30912-0004
    25 USA004 Lawrenceville Georgia United States 30046-3325
    26 USA029 Rincon Georgia United States 31326
    27 USA031 Chicago Illinois United States 60611
    28 USA073 Springfield Illinois United States 62702-4968
    29 USA074 Iowa City Iowa United States 52242-1081
    30 USA037 Kansas City Kansas United States 66160
    31 USA002 New Orleans Louisiana United States 70112
    32 USA017 Baltimore Maryland United States 21224-3057
    33 USA013 Rochester Minnesota United States 55905
    34 USA061 Saint Louis Missouri United States 63110-1035
    35 USA009 Omaha Nebraska United States 68106
    36 USA045 Omaha Nebraska United States 68124
    37 USA069 Hillsborough New Jersey United States 08844-1528
    38 USA065 Bayside New York United States 11361
    39 USA059 Bronx New York United States 10461-2720
    40 USA011 New York New York United States 10017-6739
    41 USA076 Charlotte North Carolina United States 28204
    42 USA051 Durham North Carolina United States 27710
    43 USA007 Winston-Salem North Carolina United States 27103
    44 USA064 Cincinnati Ohio United States 45267-2800
    45 USA018 Cleveland Ohio United States 44195
    46 USA063 Columbus Ohio United States 43210-1240
    47 USA075 Montgomery Ohio United States 45242-5223
    48 USA071 Portland Oregon United States 97213-2982
    49 USA025 Portland Oregon United States 97239
    50 USA015 DuBois Pennsylvania United States 15801
    51 USA040 Philadelphia Pennsylvania United States 19104
    52 USA044 Anderson South Carolina United States 29621
    53 USA024 Charleston South Carolina United States 29414
    54 USA020 Charleston South Carolina United States 29425
    55 USA012 Rock Hill South Carolina United States 29732
    56 USA022 Franklin Tennessee United States 37067
    57 USA041 Hendersonville Tennessee United States 37075
    58 USA021 McKinney Texas United States 75069
    59 USA006 San Antonio Texas United States 78258
    60 USA052 Tyler Texas United States 75708
    61 ARG004 Ciudad autónoma de Buenos Aires Buenos Aires Argentina C1426ABP
    62 ARG005 Quilmes Buenos Aires Argentina B1878FNR
    63 ARG006 Villa Vatteone Buenos Aires Argentina B1853AIK
    64 ARG002 Cordoba Córdoba Argentina 5000
    65 ARG001 Rosario Santa Fe Argentina S2000DTC
    66 ARG003 Córdoba Argentina X5003DCE
    67 AUS006 Concord New South Wales Australia 2139
    68 AUS004 New Lambton Heights New South Wales Australia 2305
    69 AUS002 Westmead New South Wales Australia 2145
    70 AUS010 Chermside Queensland Australia 4032
    71 AUS003 Greenslopes Queensland Australia 4120
    72 AUS011 Woolloongabba Queensland Australia 4102
    73 AUS008 Adelaide South Australia Australia 5000
    74 AUS007 Clayton Victoria Australia 3168
    75 AUS005 Perth Australia 5000
    76 AUT001 Linz Oberösterreich Austria 4040
    77 CAN003 Winnepeg Manitoba Canada R2H 2A6
    78 CAN004 Windsor Ontario Canada N8X-5A6
    79 CHL001 Curico Maule Chile 3440000
    80 CHL002 Quillota Chile 2260000
    81 CHL004 Talca Chile
    82 CHL003 Valparaíso Chile 2340000
    83 DNK001 Roskilde Zeeland Denmark 4000
    84 DNK004 Aalborg Denmark 9000
    85 DNK002 Aarhus N Denmark 08200
    86 DNK003 Odensa C Denmark 5000
    87 FRA012 Nice Alpes-Maritimes France 06000
    88 FRA010 Suresnes Hauts-de-Seine France 92151
    89 FRA008 Nantes Loire-Atlantique France 44000
    90 FRA006 Amiens cedex 1 France 80054
    91 FRA005 Brest France 29609
    92 FRA007 Caen France 14033
    93 FRA002 Creteil France 94000
    94 FRA001 Marseille France 13285
    95 FRA014 Paris France 75013
    96 FRA009 Paris France 75018
    97 FRA013 Paris France 75020
    98 FRA004 Saint Denis Cedex France 97405
    99 FRA003 Saint Pierre France 97448
    100 FRA011 Toulouse France 31400
    101 GER013 Gauting Bayern Germany 82131
    102 GER005 München Bayern Germany 80335
    103 GER010 Immenhausen Hessen Germany 34376
    104 GER011 Köln Nordrhein-Westfalen Germany 51109
    105 GER008 Berlin Germany 13125
    106 GER006 Dresden Germany 01307
    107 GER009 Essen Germany 45127
    108 GER002 Frankfurt Germany 69590
    109 GER004 Freiburg Germany 79106
    110 GER007 Hannover Germany 30625
    111 GRC002 Athens Attiki Greece 11527
    112 GRC001 Herakleion Greece 71110
    113 HUN002 Budapest Hungary 1121
    114 ISR008 Tel Aviv-Yafo Tel-Aviv Israel 64239
    115 ISR001 Ashkelon Israel 78100
    116 ISR007 Haifa Israel 34362
    117 ISR005 Jerusalem Israel 91120
    118 ISR003 Petah Tikva Israel 4910000
    119 ISR004 Ramat Gan Israel 52621
    120 ITA006 Modena Emilia-Romagna Italy 41124
    121 ITA008 Siena Toscana Italy 53100
    122 ITA004 Firenze Italy 50134
    123 ITA001 Milano Italy 20122
    124 ITA009 Milano Italy 20123
    125 ITA007 Monza Italy 20900
    126 ITA003 Pavia Italy 27100
    127 ITA005 Roma Italy 00168
    128 JPN011 Nagoya-shi Aiti Japan 465-0065
    129 JPN003 Fukuoka-Shi Hukuoka Japan 814-0133
    130 JPN014 Hamamatsu-shi Sizuoka Japan 434-8511
    131 JPN010 Kiyose Tokyo Japan 204-8522
    132 JPN005 Shinjuku-ku Tokyo Japan 160-8582
    133 JPN008 Shinjuku-ku Tokyo Japan 1628655
    134 JPN009 Shimonoseki Yamaguti Japan 750-8520
    135 JPN001 Fukui Japan 910-8526
    136 JPN004 Fukuoka Japan 819-8555
    137 JPN006 Nagano Japan 380-0928
    138 JPN012 Naka-gun Japan 319-1113
    139 JPN002 Sakai-shi Japan 591-8555
    140 KOR005 Seongnam-si Gyeonggido Korea, Republic of 13620
    141 KOR001 Seoul Korea, Republic of 03080
    142 KOR004 Seoul Korea, Republic of 03722
    143 KOR002 Seoul Korea, Republic of 05505
    144 KOR003 Seoul Korea, Republic of 06973
    145 NZL002 Hamilton Waikato New Zealand 3204
    146 NZL004 Auckland New Zealand 1051
    147 NZL001 Christchurch New Zealand 8461
    148 NZL003 Havelock North New Zealand 4130
    149 POL003 Kielce Swietokrzyskie Poland 25-751
    150 PRT002 Braga Portugal 4710-243
    151 PRT003 Lisboa Portugal 1796-001
    152 ESP007 Vigo Pontevedra Spain 36312
    153 ESP002 Barcelona Spain 08003
    154 ESP003 Barcelona Spain 8035
    155 ESP005 Girona Spain 17007
    156 ESP001 Madrid Spain 28034
    157 ESP004 Madrid Spain 28046
    158 ESP006 Pontevedra Spain 36001
    159 TWN004 Putzu Chiayi Taiwan 61383
    160 TWN001 Douliu Taiwan 640
    161 TWN005 Kaohsiung Taiwan 807
    162 TWN003 Kaohsiung Taiwan 813
    163 TWN007 New Taipei City Taiwan 23561
    164 TWN002 Taipei city Taiwan 116
    165 TWN006 Taipei Taiwan 10002
    166 TUR003 Izmir Turkey 35110
    167 TUR002 Kocaeli Turkey 41380
    168 GBR001 Cambridge United Kingdom CB2 OAY
    169 GBR003 London United Kingdom SW3 6NP

    Sponsors and Collaborators

    • Insmed Incorporated

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Insmed Incorporated
    ClinicalTrials.gov Identifier:
    NCT04677569
    Other Study ID Numbers:
    • INS-416
    • 2020-003079-16
    First Posted:
    Dec 21, 2020
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Insmed Incorporated
    Nontuberculous Mycobacterial Lung Infection
    Mycobacterium avium complex
    Arikayce®
    Additional relevant MeSH terms:
    Infections
    Mycobacterium Infections
    Mycobacterium Infections, Nontuberculous
    Azithromycin
    Amikacin
    Ethambutol

    Study Results

    No Results Posted as of Aug 17, 2022