Clinical trial NCT04677569: Study to Evaluate ALIS (Amikacin Liposome Inhalation Suspension) in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Mycobacterium Infections, Nontuberculous
Keywords: Nontuberculous Mycobacterial Lung Infection
Mycobacterium avium complex
Arikayce®
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 425
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Respiratory Symptom Score at Month 13
timeFrame: Baseline to Month 13
Secondary outcomes:
measure: Percentage of Participants Achieving Durable Culture Conversion at Month 15
timeFrame: Month 15
measure: Change from Baseline in Fatigue Symptom Score at Month 13
timeFrame: Baseline to Month 13
measure: Percentage of Participants Achieving Culture Conversion by Month 6
timeFrame: Month 6
measure: Percentage of Participants Achieving Culture Conversion by Month 12
timeFrame: Month 12
measure: Percentage of Participants Achieving Culture Conversion by Month 13
timeFrame: Month 13
measure: Percentage of Participants Achieving Culture Conversion During Treatment
timeFrame: Baseline to Month 12
measure: Time to Culture Conversion
timeFrame: Baseline to Month 12
measure: Time to the First Negative Culture
timeFrame: Baseline to Month 12
measure: Percentage of Participants Who Develop a Mycobacterium avium Complex (MAC) Isolate with Amikacin Minimum Inhibitory Concentration (MIC) ≥ 128 μg/mL More Than One Time
timeFrame: Baseline to Month 15
measure: 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
timeFrame: Baseline to Month 15
measure: 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
timeFrame: Baseline to Month 15
measure: 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
timeFrame: Baseline to Month 13
measure: Number of Participants Who Experience an Adverse Event (AEs)
timeFrame: Baseline to Month 15
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: USA008
state: Alabama
city: Fresno
country: United States
facility: USA062
state: California
city: Los Angeles
country: United States
facility: USA060
state: California
city: Newport Beach
country: United States
facility: USA090
state: California
city: Sacramento
country: United States
facility: USA058
state: California
city: San Diego
country: United States
facility: USA048
state: California
city: San Francisco
country: United States
facility: USA081
state: California
city: Santa Barbara
country: United States
facility: USA055
state: California
city: Stanford
country: United States
facility: USA050
state: California
city: Denver
country: United States
facility: USA001
state: Colorado
city: Washington
country: United States
facility: USA023
state: District of Columbia
city: Bradenton
country: United States
facility: USA080
state: Florida
city: Brandon
country: United States
facility: USA028
state: Florida
city: Clearwater
country: United States
facility: USA003
state: Florida
city: Jacksonville
country: United States
facility: USA043
state: Florida
city: Jacksonville
country: United States
facility: USA072
state: Florida
city: Jacksonville
country: United States
facility: USA085
state: Florida
city: Jacksonville
country: United States
facility: USA047
state: Florida
city: Kissimmee
country: United States
facility: USA042
state: Florida
city: Naples
country: United States
facility: USA039
state: Florida
city: Naples
country: United States
facility: USA096
state: Florida
city: Naples
country: United States
facility: USA097
state: Florida
city: New Port Richey
country: United States
facility: USA046
state: Florida
city: Saint Petersburg
country: United States
facility: USA070
state: Florida
city: Saint Petersburg
country: United States
facility: USA014
state: Florida
city: Sarasota
country: United States
facility: USA054
state: Florida
city: Sebastian
country: United States
facility: USA084
state: Florida
city: Sebring
country: United States
facility: USA026
state: Florida
city: Tampa
country: United States
facility: USA067
state: Florida
city: Tampa
country: United States
facility: USA068
state: Florida
city: Weston
country: United States
facility: USA053
state: Florida
city: Atlanta
country: United States
facility: USA038
state: Georgia
city: Augusta
country: United States
facility: USA066
state: Georgia
city: Lawrenceville
country: United States
facility: USA004
state: Georgia
city: Rincon
country: United States
facility: USA029
state: Georgia
city: Coeur d'Alene
country: United States
facility: USA079
state: Idaho
city: Chicago
country: United States
facility: USA031
state: Illinois
city: Springfield
country: United States
facility: USA073
state: Illinois
city: Springfield
country: United States
facility: USA030
state: Illinois
city: Iowa City
country: United States
facility: USA074
state: Iowa
city: Kansas City
country: United States
facility: USA037
state: Kansas
city: New Orleans
country: United States
facility: USA002
state: Louisiana
city: Baltimore
country: United States
facility: USA017
state: Maryland
city: Lexington
country: United States
facility: USA099
state: Massachusetts
city: Springfield
country: United States
facility: USA077
state: Massachusetts
city: Rochester
country: United States
facility: USA013
state: Minnesota
city: Columbia
country: United States
facility: USA082
state: Missouri
city: Saint Louis
country: United States
facility: USA061
state: Missouri
city: Omaha
country: United States
facility: USA045
state: Nebraska
city: Omaha
country: United States
facility: USA009
state: Nebraska
city: Hillsborough
country: United States
facility: USA069
state: New Jersey
city: Toms River
country: United States
facility: USA032
state: New Jersey
city: Bayside
country: United States
facility: USA065
state: New York
city: Bronx
country: United States
facility: USA059
state: New York
city: East Syracuse
country: United States
facility: USA088
state: New York
city: New York
country: United States
facility: USA011
state: New York
city: Charlotte
country: United States
facility: USA076
state: North Carolina
city: Charlotte
country: United States
facility: USA035
state: North Carolina
city: Charlotte
country: United States
facility: USA033
state: North Carolina
city: Durham
country: United States
facility: USA051
state: North Carolina
city: Mooresville
country: United States
facility: USA034
state: North Carolina
city: Winston-Salem
country: United States
facility: USA007
state: North Carolina
city: Cincinnati
country: United States
facility: USA075
state: Ohio
city: Cincinnati
country: United States
facility: USA064
state: Ohio
city: Cleveland
country: United States
facility: USA018
state: Ohio
city: Columbus
country: United States
facility: USA063
state: Ohio
city: Portland
country: United States
facility: USA071
state: Oregon
city: Portland
country: United States
facility: USA025
state: Oregon
city: DuBois
country: United States
facility: USA015
state: Pennsylvania
city: Philadelphia
country: United States
facility: USA040
state: Pennsylvania
city: Philadelphia
country: United States
facility: USA093
state: Pennsylvania
city: Providence
country: United States
facility: USA092
state: Rhode Island
city: Anderson
country: United States
facility: USA044
state: South Carolina
city: Charleston
country: United States
facility: USA024
state: South Carolina
city: Charleston
country: United States
facility: USA020
state: South Carolina
city: Rock Hill
country: United States
facility: USA012
state: South Carolina
city: Franklin
country: United States
facility: USA022
state: Tennessee
city: Hendersonville
country: United States
facility: USA041
state: Tennessee
city: Nashville
country: United States
facility: USA078
state: Tennessee
city: Dallas
country: United States
facility: USA016
state: Texas
city: Dallas
country: United States
facility: USA100
state: Texas
city: Denison
country: United States
facility: USA091
state: Texas
city: Houston
country: United States
facility: USA086
state: Texas
city: McKinney
country: United States
facility: USA021
state: Texas
city: San Antonio
country: United States
facility: USA006
state: Texas
city: Temple
country: United States
facility: USA019
state: Texas
city: Temple
country: United States
facility: USA089
state: Texas
city: Tyler
country: United States
facility: USA052
state: Texas
city: Charlottesville
country: United States
facility: USA083
state: Virginia
city: Madison
country: United States
facility: USA087
state: Wisconsin
city: Ciudad autÃ³noma de Buenos Aires
country: Argentina
facility: ARG004
state: Buenos Aires
city: Quilmes
country: Argentina
facility: ARG005
state: Buenos Aires
city: Villa Vatteone
country: Argentina
facility: ARG006
state: Buenos Aires
city: Rosario
country: Argentina
facility: ARG001
state: Santa Fe
city: San Miguel de Tucumán
country: Argentina
facility: ARG007
state: Tucumán
city: Cordoba
country: Argentina
facility: ARG002
city: Cordoba
country: Argentina
facility: ARG003
city: Concord
country: Australia
facility: AUS006
state: New South Wales
city: New Lambton Heights
country: Australia
facility: AUS004
state: New South Wales
city: Westmead
country: Australia
facility: AUS002
state: New South Wales
city: Birtinya
country: Australia
facility: AUS012
state: Queensland
city: Chermside
country: Australia
facility: AUS010
state: Queensland
city: Douglas
country: Australia
facility: AUS013
state: Queensland
city: Greenslopes
country: Australia
facility: AUS003
state: Queensland
city: Herston
country: Australia
facility: AUS016
state: Queensland
city: Meadowbrook
country: Australia
facility: AUS014
state: Queensland
city: South Brisbane
country: Australia
facility: AUS001
state: Queensland
city: Woolloongabba
country: Australia
facility: AUS011
state: Queensland
city: Adelaide
country: Australia
facility: AUS008
state: South Australia
city: Clayton
country: Australia
facility: AUS007
state: Victoria
city: Melbourne
country: Australia
facility: AUS009
state: Victoria
city: Spearwood
country: Australia
facility: AUS015
state: Western Australia
city: Perth
country: Australia
facility: AUS005
city: Wels
country: Austria
facility: AUT003
state: OberÃ¶sterreich
city: Linz
country: Austria
facility: AUT001
state: Oberösterreich
city: Bruxelles
country: Belgium
facility: BEL003
state: Brussels
city: Ghent
country: Belgium
facility: BEL002
city: Leuven
country: Belgium
facility: BEL001
city: Winnepeg
country: Canada
facility: CAN003
state: Manitoba
city: Toronto
country: Canada
facility: CAN002
state: Ontario
city: Windsor
country: Canada
facility: CAN004
state: Ontario
city: Curico
country: Chile
facility: CHL001
state: Maule
city: Quillota
country: Chile
facility: CHL002
city: Talca
country: Chile
facility: CHL004
city: Valparaíso
country: Chile
facility: CHL003
city: Vejle
country: Denmark
facility: DNK005
state: South Denmark
city: Roskilde
country: Denmark
facility: DNK001
state: Zeeland
city: Aalborg
country: Denmark
facility: DNK004
city: Aarhus N
country: Denmark
facility: DNK002
city: Odensa C
country: Denmark
facility: DNK003
city: Nice
country: France
facility: FRA012
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: FRA016
state: Bas-Rhin
city: Pessac
country: France
facility: FRA015
state: Gironde
city: Suresnes
country: France
facility: FRA010
state: Hauts-de-Seine
city: Nantes
country: France
facility: FRA008
state: Loire-Atlantique
city: Amiens cedex 1
country: France
facility: FRA006
city: Brest
country: France
facility: FRA005
city: Caen
country: France
facility: FRA007
city: Creteil
country: France
facility: FRA002
city: Marseille
country: France
facility: FRA001
city: Paris
country: France
facility: FRA014
city: Paris
country: France
facility: FRA009
city: Paris
country: France
facility: FRA013
city: Saint Denis Cedex
country: France
facility: FRA004
city: Saint Pierre
country: France
facility: FRA003
city: Toulouse
country: France
facility: FRA011
city: Donaustauf
country: Germany
facility: GER001
state: Bayern
city: Gauting
country: Germany
facility: GER013
state: Bayern
city: München
country: Germany
facility: GER005
state: Bayern
city: Potsdam
country: Germany
facility: GER012
state: Brandenburg
city: Immenhausen
country: Germany
facility: GER010
state: Hessen
city: Borstel
country: Germany
facility: GER003
state: Niedersachsen
city: Köln
country: Germany
facility: GER014
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: GER011
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GER008
city: Dresden
country: Germany
facility: GER006
city: Essen
country: Germany
facility: GER009
city: Frankfurt
country: Germany
facility: GER002
city: Freiburg
country: Germany
facility: GER004
city: Hannover
country: Germany
facility: GER007
city: Athens
country: Greece
facility: GRC002
state: Attiki
city: Alexandroupolis
country: Greece
facility: GRC003
city: Herakleion
country: Greece
facility: GRC001
city: Budapest
country: Hungary
facility: HUN002
city: Torokbalint
country: Hungary
facility: HUN001
city: Tel Aviv-Yafo
country: Israel
facility: ISR008
state: Tel-Aviv
city: Ashkelon
country: Israel
facility: ISR001
city: Haifa
country: Israel
facility: ISR007
city: Isr002
country: Israel
facility: ISR002
city: Jerusalem
country: Israel
facility: ISR005
city: Petah Tikva
country: Israel
facility: ISR003
city: Ramat Gan
country: Israel
facility: ISR004
city: Modena
country: Italy
facility: ITA006
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: ITA011
state: Emilia-Romagna
city: Genova
country: Italy
facility: ITA010
state: Liguria
city: Milan
country: Italy
facility: ITA002
state: Milano
city: Siena
country: Italy
facility: ITA008
state: Toscana
city: Firenze
country: Italy
facility: ITA004
city: Milano
country: Italy
facility: ITA001
city: Milano
country: Italy
facility: ITA009
city: Monza
country: Italy
facility: ITA007
city: Pavia
country: Italy
facility: ITA003
city: Roma
country: Italy
facility: ITA005
city: Nagoya-shi
country: Japan
facility: JPN011
state: Aiti
city: Kita Kyushu-shi
country: Japan
facility: JPN020
state: Hukuoka
city: Yokohama-Shi Tsuzuki-Ku
country: Japan
facility: JPN022
state: Kanagawa
city: Matsusaka-Shi
country: Japan
facility: JPN017
state: Mie
city: Nagasaki-Shi
country: Japan
facility: JPN018
state: Nagasaki
city: Kurashiki-Shi
country: Japan
facility: JPN023
state: Okayama
city: Izumo-Shi
country: Japan
facility: JPN019
state: Simane
city: Hamamatsu-shi
country: Japan
facility: JPN014
state: Sizuoka
city: Kiyose-Shi
country: Japan
facility: JPN015
state: Tokyo
city: Ota-Ku
country: Japan
facility: JPN021
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: JPN008
state: Tokyo
city: Fukui
country: Japan
facility: JPN001
city: Fukuoka
country: Japan
facility: JPN004
city: Jonan-ku
country: Japan
facility: JPN003
city: Kiyose
country: Japan
facility: JPN010
city: Nagano
country: Japan
facility: JPN006
city: Naka-gun
country: Japan
facility: JPN012
city: Sakai-shi
country: Japan
facility: JPN002
city: Shimonoseki
country: Japan
facility: JPN009
city: Tokyo
country: Japan
facility: JPN005
city: Toyonaka-Shi
country: Japan
facility: JPN016
state: Ôsaka
city: Seongnam-si
country: Korea, Republic of
facility: KOR005
state: Gyeonggido
city: Seongbuk-Gu
country: Korea, Republic of
facility: KOR007
state: Seoul Teugbyeolsi
city: Ansan-si
country: Korea, Republic of
facility: KOR008
city: Incheon
country: Korea, Republic of
facility: KOR006
city: Seoul
country: Korea, Republic of
facility: KOR004
city: Seoul
country: Korea, Republic of
facility: KOR002
city: Seoul
country: Korea, Republic of
facility: KOR009
city: Seoul
country: Korea, Republic of
facility: KOR003
city: Seoul
country: Korea, Republic of
facility: KOR001
city: Hastings
country: New Zealand
facility: NZL003
state: Hawkes's Bay
city: Hamilton
country: New Zealand
facility: NZL002
state: Waikato
city: Auckland
country: New Zealand
facility: NZL004
city: Christchurch
country: New Zealand
facility: NZL001
city: Kielce
country: Poland
facility: POL003
state: Swietokrzyskie
city: Braga
country: Portugal
facility: PRT002
city: Lisboa
country: Portugal
facility: PRT003
city: L'hospitalet De Llobregat
country: Spain
facility: ESP009
state: Barcelona
city: Vigo
country: Spain
facility: ESP007
state: Pontevedra
city: Barcelona
country: Spain
facility: ESP002
city: Barcelona
country: Spain
facility: ESP008
city: Barcelona
country: Spain
facility: ESP003
city: Girona
country: Spain
facility: ESP005
city: Madrid
country: Spain
facility: ESP010
city: Madrid
country: Spain
facility: ESP001
city: Madrid
country: Spain
facility: ESP004
city: Pamplona
country: Spain
facility: ESP011
city: Pontevedra
country: Spain
facility: ESP006
city: Sevilla
country: Spain
facility: ESP012
city: Chiayi
country: Taiwan
facility: TWN004
city: Douliu
country: Taiwan
facility: TWN001
city: Hsinchu City
country: Taiwan
facility: TWN012
city: Kaohsiung
country: Taiwan
facility: TWN005
city: Kaohsiung
country: Taiwan
facility: TWN003
city: New Taipei City
country: Taiwan
facility: TWN007
city: Taipei City
country: Taiwan
facility: TWN011
city: Taipei city
country: Taiwan
facility: TWN002
city: Taipei
country: Taiwan
facility: TWN006
city: Taipei
country: Taiwan
facility: TWN010
city: Taipei
country: Taiwan
facility: TWN008
city: Taipei
country: Taiwan
facility: TWN009
city: Izmir
country: Turkey
facility: TUR003
city: Kocaeli
country: Turkey
facility: TUR002
city: Maltepe
country: Turkey
facility: TUR004
city: Plymouth
country: United Kingdom
facility: GBR009
state: Devon
city: Salford
country: United Kingdom
facility: GBR012
state: Lancashire
city: Swansea
country: United Kingdom
facility: GBR013
state: West Glamorgan
city: Birmingham
country: United Kingdom
facility: GBR008
state: West Midlands
city: Aberdeen
country: United Kingdom
facility: GBR005
city: Cambridge
country: United Kingdom
facility: GBR001
city: Dundee
country: United Kingdom
facility: GBR002
city: Liverpool
country: United Kingdom
facility: GBR004
city: London
country: United Kingdom
facility: GBR007
city: London
country: United Kingdom
facility: GBR010
city: London
country: United Kingdom
facility: GBR003
Study officials:
References: