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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04677569




Registration number
NCT04677569
Ethics application status
Date submitted
16/12/2020
Date registered
21/12/2020

Titles & IDs
Public title
Study to Evaluate ALIS (Amikacin Liposome Inhalation Suspension) in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex
Scientific 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
Secondary ID [1] 0 0
2020-003079-16
Secondary ID [2] 0 0
INS-416
Universal Trial Number (UTN)
Trial acronym
ENCORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mycobacterium Infections, Nontuberculous 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ALIS
Treatment: Drugs - Azithromycin
Treatment: Drugs - Ethambutol
Treatment: Drugs - ELC (matching placebo for ALIS)

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.

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.


Treatment: Drugs: ALIS
Inhalation via nebulization over approximately 6 to 15 minutes

Treatment: Drugs: Azithromycin
Oral tablet

Treatment: Drugs: Ethambutol
Oral tablet

Treatment: Drugs: ELC (matching placebo for ALIS)
Inhalation via nebulization over approximately 6 to 15 minutes
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Respiratory Symptom Score at Month 13
Timepoint [1] 0 0
Baseline to Month 13
Secondary outcome [1] 0 0
Percentage of Participants Achieving Durable Culture Conversion at Month 15
Timepoint [1] 0 0
Month 15
Secondary outcome [2] 0 0
Change from Baseline in Fatigue Symptom Score at Month 13
Timepoint [2] 0 0
Baseline to Month 13
Secondary outcome [3] 0 0
Percentage of Participants Achieving Culture Conversion by Month 12
Timepoint [3] 0 0
Month 12
Secondary outcome [4] 0 0
Percentage of Participants Achieving Culture Conversion by Month 6
Timepoint [4] 0 0
Month 6
Secondary outcome [5] 0 0
Percentage of Participants Achieving Culture Conversion During Treatment
Timepoint [5] 0 0
Baseline to Month 12
Secondary outcome [6] 0 0
Time to Culture Conversion
Timepoint [6] 0 0
Baseline to Month 12
Secondary outcome [7] 0 0
Time to the First Negative Culture
Timepoint [7] 0 0
Baseline to Month 12
Secondary outcome [8] 0 0
Percentage of Participants Who Develop a Mycobacterium avium Complex (MAC) Isolate with Amikacin Minimum Inhibitory Concentration (MIC) = 128 µg/mL More Than One Time
Timepoint [8] 0 0
Baseline to Month 15
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Baseline to Month 15
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline to Month 15
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Baseline to Month 15
Secondary outcome [12] 0 0
Number of Participants Who Experience an Adverse Event (AEs)
Timepoint [12] 0 0
Baseline to Month 15

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/08/2023
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
AUS006 - Concord
Recruitment hospital [2] 0 0
AUS004 - New Lambton Heights
Recruitment hospital [3] 0 0
AUS002 - Westmead
Recruitment hospital [4] 0 0
AUS012 - Birtinya
Recruitment hospital [5] 0 0
AUS010 - Chermside
Recruitment hospital [6] 0 0
AUS003 - Greenslopes
Recruitment hospital [7] 0 0
AUS016 - Herston
Recruitment hospital [8] 0 0
AUS014 - Meadowbrook
Recruitment hospital [9] 0 0
AUS011 - Woolloongabba
Recruitment hospital [10] 0 0
AUS008 - Adelaide
Recruitment hospital [11] 0 0
AUS007 - Clayton
Recruitment hospital [12] 0 0
AUS005 - Perth
Recruitment hospital [13] 0 0
AUS015 - Spearwood
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4575 - Birtinya
Recruitment postcode(s) [5] 0 0
4032 - Chermside
Recruitment postcode(s) [6] 0 0
4120 - Greenslopes
Recruitment postcode(s) [7] 0 0
4029 - Herston
Recruitment postcode(s) [8] 0 0
4131 - Meadowbrook
Recruitment postcode(s) [9] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 0 0
5000 - Adelaide
Recruitment postcode(s) [11] 0 0
3168 - Clayton
Recruitment postcode(s) [12] 0 0
5000 - Perth
Recruitment postcode(s) [13] 0 0
6163 - Spearwood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
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Colorado
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United States of America
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District of Columbia
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United States of America
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Florida
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Georgia
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Idaho
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Illinois
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Iowa
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Kansas
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United States of America
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Louisiana
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Maryland
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Massachusetts
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Minnesota
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Missouri
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Nebraska
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New Jersey
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New York
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North Carolina
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Ohio
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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Tennessee
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Córdoba
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Argentina
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Santa Fe
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Argentina
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Tucumán
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Austria
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Oberösterreich
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Belgium
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Brussels
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Belgium
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Ghent
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Belgium
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Leuven
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Canada
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Manitoba
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Canada
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Ontario
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Chile
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Maule
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Chile
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Quillota
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Chile
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Valparaiso
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Denmark
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Zeeland
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Denmark
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Aalborg
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Denmark
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Aarhus N
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Denmark
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Odensa C
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France
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Alpes-Maritimes
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France
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Bas-Rhin
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France
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Gironde
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France
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Hauts-de-Seine
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France
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Loire-Atlantique
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France
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Amiens cedex 1
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France
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Brest
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France
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Caen
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Creteil
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Marseille
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France
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Paris
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Saint Denis Cedex
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France
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Saint Pierre
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France
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Toulouse
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Nordrhein-Westfalen
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Essen
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Germany
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Freiburg
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Germany
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Hannover
Country [66] 0 0
Greece
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Attiki
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Hungary
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Budapest
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Israel
State/province [68] 0 0
Tel-Aviv
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Israel
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Ashkelon
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Italy
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Emilia-Romagna
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Italy
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Firenze
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Italy
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Milano
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Italy
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Monza
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Italy
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Pavia
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Italy
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Roma
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Japan
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Aiti
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Japan
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Mie
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Japan
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Nagasaki
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Japan
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Simane
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Japan
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Sizuoka
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Japan
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Tokyo
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Japan
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Fukui
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Japan
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Fukuoka
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Japan
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Jonan-ku
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Japan
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Kiyose
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Japan
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Nagano
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Japan
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Naka-gun
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Japan
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Sakai-shi
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Japan
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Shimonoseki
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Japan
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Ôsaka
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
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Seoul Teugbyeolsi
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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New Zealand
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Hawkes's Bay
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New Zealand
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Waikato
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Poland
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Swietokrzyskie
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Portugal
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Braga
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Portugal
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Lisboa
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Spain
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Barcelona
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Spain
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Pontevedra
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Spain
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Girona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Sevilla
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Taiwan
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Chiayi
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Taiwan
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Douliu
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Taiwan
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Kaohsiung
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Taiwan
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New Taipei City
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Taiwan
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Taipei city
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Taiwan
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Taipei
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Turkey
State/province [118] 0 0
Istanbul
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Turkey
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Izmir
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Turkey
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Kocaeli
Country [121] 0 0
United Kingdom
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Devon
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United Kingdom
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Lancashire
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United Kingdom
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West Glamorgan
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United Kingdom
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West Midlands
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United Kingdom
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Aberdeen
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United Kingdom
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Cambridge
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United Kingdom
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Dundee
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Liverpool
Country [129] 0 0
United Kingdom
State/province [129] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Insmed Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Insmed Medical Information
Address 0 0
Country 0 0
Phone 0 0
844-4-INSMED
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04677569