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

Mycobacterium Infections, Nontuberculous Clinical Trial

— ENCORE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04677569
• Other study ID #: INS-416
• Secondary ID: 2020-003079-16
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2021
• Est. completion date: August 21, 2023

Study information

• Verified date: August 2023
• Source: Insmed Incorporated
• Contact: Insmed Medical Information
• Phone: 844-4-INSMED
• Email: medicalinformation[@]insmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: August 21, 2023
• Est. primary completion date: August 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infections
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous

Intervention

Drug:
• ALIS
Inhalation via nebulization over approximately 6 to 15 minutes
• Azithromycin
Oral tablet
• Ethambutol
Oral tablet
• ELC (matching placebo for ALIS)
Inhalation via nebulization over approximately 6 to 15 minutes

Locations

Country	Name	City	State
Argentina	ARG004	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	ARG002	Cordoba	Córdoba
Argentina	ARG003	Córdoba
Argentina	ARG005	Quilmes	Buenos Aires
Argentina	ARG001	Rosario	Santa Fe
Argentina	ARG007	San Miguel de Tucumán	Tucumán
Argentina	ARG006	Villa Vatteone	Buenos Aires
Australia	AUS008	Adelaide	South Australia
Australia	AUS012	Birtinya	Queensland
Australia	AUS010	Chermside	Queensland
Australia	AUS007	Clayton	Victoria
Australia	AUS006	Concord	New South Wales
Australia	AUS003	Greenslopes	Queensland
Australia	AUS016	Herston	Queensland
Australia	AUS014	Meadowbrook	Queensland
Australia	AUS004	New Lambton Heights	New South Wales
Australia	AUS005	Perth	Western Australia
Australia	AUS015	Spearwood	Western Australia
Australia	AUS002	Westmead	New South Wales
Australia	AUS011	Woolloongabba	Queensland
Austria	AUT001	Linz	Oberösterreich
Belgium	BEL003	Bruxelles	Brussels
Belgium	BEL002	Ghent
Belgium	BEL001	Leuven
Canada	CAN002	Toronto	Ontario
Canada	CAN004	Windsor	Ontario
Canada	CAN003	Winnepeg	Manitoba
Chile	CHL001	Curico	Maule
Chile	CHL002	Quillota
Chile	CHL003	Valparaiso
Denmark	DNK004	Aalborg
Denmark	DNK002	Aarhus N
Denmark	DNK003	Odensa C
Denmark	DNK001	Roskilde	Zeeland
France	FRA006	Amiens cedex 1
France	FRA005	Brest
France	FRA007	Caen
France	FRA002	Creteil
France	FRA001	Marseille
France	FRA008	Nantes	Loire-Atlantique
France	FRA012	Nice	Alpes-Maritimes
France	FRA009	Paris
France	FRA013	Paris
France	FRA014	Paris
France	FRA015	Pessac	Gironde
France	FRA004	Saint Denis Cedex
France	FRA003	Saint Pierre
France	FRA016	Strasbourg	Bas-Rhin
France	FRA010	Suresnes	Hauts-de-Seine
France	FRA011	Toulouse
Germany	GER008	Berlin
Germany	GER006	Dresden
Germany	GER009	Essen
Germany	GER004	Freiburg
Germany	GER013	Gauting	Bayern
Germany	GER007	Hannover
Germany	GER010	Immenhausen	Hessen
Germany	GER011	Köln	Nordrhein-Westfalen
Germany	GER014	Köln	Nordrhein-Westfalen
Germany	GER005	München	Bayern
Greece	GRC002	Athens	Attiki
Hungary	HUN002	Budapest
Israel	ISR001	Ashkelon
Israel	ISR007	Haifa
Israel	ISR005	Jerusalem
Israel	ISR003	Petah Tikva
Israel	ISR004	Ramat Gan
Israel	ISR008	Tel Aviv-Yafo	Tel-Aviv
Italy	ITA004	Firenze
Italy	ITA001	Milano
Italy	ITA009	Milano
Italy	ITA006	Modena	Emilia-Romagna
Italy	ITA007	Monza
Italy	ITA003	Pavia
Italy	ITA005	Roma
Japan	JPN001	Fukui
Japan	JPN004	Fukuoka
Japan	JPN014	Hamamatsu-shi	Sizuoka
Japan	JPN019	Izumo-Shi	Simane
Japan	JPN003	Jonan-ku
Japan	JPN010	Kiyose
Japan	JPN015	Kiyose-Shi	Tokyo
Japan	JPN017	Matsusaka-Shi	Mie
Japan	JPN006	Nagano
Japan	JPN018	Nagasaki-Shi	Nagasaki
Japan	JPN011	Nagoya-shi	Aiti
Japan	JPN012	Naka-gun
Japan	JPN002	Sakai-shi
Japan	JPN009	Shimonoseki
Japan	JPN008	Shinjuku-ku	Tokyo
Japan	JPN005	Tokyo
Japan	JPN016	Toyonaka-Shi	Ôsaka
Korea, Republic of	KOR008	Ansan-si	Gyeonggido
Korea, Republic of	KOR006	Incheon
Korea, Republic of	KOR007	Seongbuk-Gu	Seoul Teugbyeolsi
Korea, Republic of	KOR005	Seongnam-si	Gyeonggido
Korea, Republic of	KOR001	Seoul
Korea, Republic of	KOR002	Seoul
Korea, Republic of	KOR003	Seoul
Korea, Republic of	KOR004	Seoul
Korea, Republic of	KOR009	Seoul
New Zealand	NZL004	Auckland
New Zealand	NZL001	Christchurch
New Zealand	NZL002	Hamilton	Waikato
New Zealand	NZL003	Hastings	Hawkes's Bay
Poland	POL003	Kielce	Swietokrzyskie
Portugal	PRT002	Braga
Portugal	PRT003	Lisboa
Spain	ESP002	Barcelona
Spain	ESP003	Barcelona
Spain	ESP008	Barcelona
Spain	ESP005	Girona
Spain	ESP009	L'hospitalet De Llobregat	Barcelona
Spain	ESP001	Madrid
Spain	ESP004	Madrid
Spain	ESP010	Madrid
Spain	ESP011	Pamplona
Spain	ESP006	Pontevedra
Spain	ESP012	Sevilla
Spain	ESP007	Vigo	Pontevedra
Taiwan	TWN004	Chiayi
Taiwan	TWN001	Douliu
Taiwan	TWN003	Kaohsiung
Taiwan	TWN005	Kaohsiung
Taiwan	TWN007	New Taipei City
Taiwan	TWN008	Taipei
Taiwan	TWN002	Taipei city
Turkey	TUR003	Izmir
Turkey	TUR002	Kocaeli
Turkey	TUR004	Maltepe	Istanbul
United Kingdom	GBR005	Aberdeen
United Kingdom	GBR008	Birmingham	West Midlands
United Kingdom	GBR001	Cambridge
United Kingdom	GBR002	Dundee
United Kingdom	GBR004	Liverpool
United Kingdom	GBR003	London
United Kingdom	GBR007	London
United Kingdom	GBR010	London
United Kingdom	GBR009	Plymouth	Devon
United Kingdom	GBR012	Salford	Lancashire
United Kingdom	GBR013	Swansea	West Glamorgan
United States	USA044	Anderson	South Carolina
United States	USA038	Atlanta	Georgia
United States	USA066	Augusta	Georgia
United States	USA017	Baltimore	Maryland
United States	USA065	Bayside	New York
United States	USA008	Birmingham	Alabama
United States	USA080	Bradenton	Florida
United States	USA059	Bronx	New York
United States	USA020	Charleston	South Carolina
United States	USA024	Charleston	South Carolina
United States	USA076	Charlotte	North Carolina
United States	USA083	Charlottesville	Virginia
United States	USA031	Chicago	Illinois
United States	USA064	Cincinnati	Ohio
United States	USA075	Cincinnati	Ohio
United States	USA003	Clearwater	Florida
United States	USA018	Cleveland	Ohio
United States	USA079	Coeur d'Alene	Idaho
United States	USA082	Columbia	Missouri
United States	USA063	Columbus	Ohio
United States	USA091	Denison	Texas
United States	USA001	Denver	Colorado
United States	USA022	Franklin	Tennessee
United States	USA062	Fresno	California
United States	USA041	Hendersonville	Tennessee
United States	USA069	Hillsborough	New Jersey
United States	USA086	Houston	Texas
United States	USA074	Iowa City	Iowa
United States	USA047	Jacksonville	Florida
United States	USA085	Jacksonville	Florida
United States	USA037	Kansas City	Kansas
United States	USA042	Kissimmee	Florida
United States	USA060	Los Angeles	California
United States	USA021	McKinney	Texas
United States	USA078	Nashville	Tennessee
United States	USA002	New Orleans	Louisiana
United States	USA046	New Port Richey	Florida
United States	USA011	New York	New York
United States	USA090	Newport Beach	California
United States	USA009	Omaha	Nebraska
United States	USA040	Philadelphia	Pennsylvania
United States	USA025	Portland	Oregon
United States	USA029	Rincon	Georgia
United States	USA013	Rochester	Minnesota
United States	USA012	Rock Hill	South Carolina
United States	USA058	Sacramento	California
United States	USA061	Saint Louis	Missouri
United States	USA014	Saint Petersburg	Florida
United States	USA006	San Antonio	Texas
United States	USA048	San Diego	California
United States	USA081	San Francisco	California
United States	USA055	Santa Barbara	California
United States	USA054	Sarasota	Florida
United States	USA073	Springfield	Illinois
United States	USA077	Springfield	Massachusetts
United States	USA050	Stanford	California
United States	USA088	Syracuse	New York
United States	USA067	Tampa	Florida
United States	USA068	Tampa	Florida
United States	USA052	Tyler	Texas
United States	USA084	Vero Beach	Florida
United States	USA023	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Respiratory Symptom Score at Month 13		Baseline to Month 13
Secondary	Percentage of Participants Achieving Durable Culture Conversion at Month 15		Month 15
Secondary	Change from Baseline in Fatigue Symptom Score at Month 13		Baseline to Month 13
Secondary	Percentage of Participants Achieving Culture Conversion by Month 12		Month 12
Secondary	Percentage of Participants Achieving Culture Conversion by Month 6		Month 6
Secondary	Percentage of Participants Achieving Culture Conversion During Treatment		Baseline to Month 12
Secondary	Time to Culture Conversion		Baseline to Month 12
Secondary	Time to the First Negative Culture		Baseline to Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants Who Experience an Adverse Event (AEs)		Baseline to Month 15