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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04677543




Registration number
NCT04677543
Ethics application status
Date submitted
16/12/2020
Date registered
21/12/2020

Titles & IDs
Public title
Validation of Patient Reported Outcome Measures 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 Validate Patient-Reported Outcome Instruments in Adult Subjects With Newly Diagnosed Nontuberculous Mycobacterial (NTM) Lung Infection Caused by Mycobacterium Avium Complex (MAC)
Secondary ID [1] 0 0
2020-002545-42
Secondary ID [2] 0 0
INS-415
Universal Trial Number (UTN)
Trial acronym
ARISE
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
Infection 0 0 0 0
Sexually transmitted infections

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

Active comparator: ALIS + Background Regimen (Azithromycin + Ethambutol) - Participants will be administered 590 mg of ALIS (amikacin liposome inhalation suspension) once daily. Participants will also be administered the background regimen of azithromycin 250 mg and ethambutol 15 mg/kg tablets orally, once daily.

Placebo comparator: ELC + Background Regimen (Azithromycin + Ethambutol) - Participants will be administered ELC (empty liposome control), a matching placebo to ALIS, once daily. Participants will also be administered the background regimen of azithromycin 250 mg and ethambutol 15 mg/kg tablets orally, 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
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
Psychometric Cross-Sectional Validation of Patient Reported Outcome (PRO): Patient Global Impression of Severity (PGI-S) Respiratory Scale Score at Baseline
Timepoint [1] 0 0
Baseline
Primary outcome [2] 0 0
Psychometric Cross-Sectional Validation of PRO: PGI-S Fatigue Scale Score at Baseline
Timepoint [2] 0 0
Baseline
Primary outcome [3] 0 0
Psychometric Cross-Sectional Validation of PRO: Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms Scale Score at Baseline
Timepoint [3] 0 0
Baseline
Primary outcome [4] 0 0
Psychometric Cross-Sectional Validation of PRO: Patient-Reported Outcome Measurement Information System - Fatigue-Short Form 7a (PROMIS F-SF 7a) Score at Baseline
Timepoint [4] 0 0
Baseline
Primary outcome [5] 0 0
Assessment of Test-Retest Reliability (TRTR) Reported as the Intraclass Co-relation (ICC) Estimate Among Participants Reporting no Change on Respiratory PGI-S Score Applied to QOL-B Respiratory Domain Score Between Screening and Baseline
Timepoint [5] 0 0
From Screening to Baseline (Day -70 to Day 1)
Primary outcome [6] 0 0
Assessment of TRTR Reported as the ICC Estimate Among Participants Reporting no Change on Fatigue PGI-S Score Applied to PROMIS F-SF 7a Score Between Screening and Baseline
Timepoint [6] 0 0
From Screening to Baseline (Day -70 to Day 1)
Primary outcome [7] 0 0
Response Rate as Assessed by Within-Subject Meaningful Change (WSMC) for QOL-B Respiratory Symptoms Final Score Estimated Via Anchor-Based Methods and Validated Via Empirical Cumulative Distribution Functions (eCDFs)
Timepoint [7] 0 0
Baseline to Month 7
Primary outcome [8] 0 0
Response Rate as Assessed by WSMC for PROMIS Fatigue Final Score Estimated Via Anchor-Based Methods and Validated Via eCDFs
Timepoint [8] 0 0
Baseline to Month 7
Secondary outcome [1] 0 0
Percentage of Participants Achieving Culture Conversion by Month 6
Timepoint [1] 0 0
Baseline to Month 6
Secondary outcome [2] 0 0
Change From Baseline in QOL-B Respiratory Symptom Score at Month 7
Timepoint [2] 0 0
Baseline to Month 7
Secondary outcome [3] 0 0
Change From Baseline in PROMIS F-SF 7a Score at Month 7
Timepoint [3] 0 0
Baseline to Month 7
Secondary outcome [4] 0 0
Time to First Culture Conversion
Timepoint [4] 0 0
Baseline to Month 6
Secondary outcome [5] 0 0
Time to First Negative Culture
Timepoint [5] 0 0
Baseline to Month 7
Secondary outcome [6] 0 0
Percentage of Participants Who Develop a MAC Isolate With Amikacin Minimum Inhibitory Concentration (MIC) = 128 Micrograms Per Millliliter (µg/mL) at More Than 1 Visit
Timepoint [6] 0 0
Up to Month 7
Secondary outcome [7] 0 0
Recurrence of MAC (Relapse) Assessed as Percentage of Participants Who Achieved Culture Conversion With a Subsequent at Least One MAC Positive Culture in Agar Media or Broth Media in at Least 2 Consecutive Visits
Timepoint [7] 0 0
Baseline to Month 7
Secondary outcome [8] 0 0
Recurrence of MAC (New Infection) Assessed as Percentage of Participants Who Achieved Culture Conversion With a Subsequent at Least One MAC Positive Culture in Agar Media or Broth Media in at Least 2 Consecutive Visits
Timepoint [8] 0 0
Baseline to Month 7
Secondary outcome [9] 0 0
Number of Participants Who Experience Any Treatment-emergent Adverse Event (TEAE)
Timepoint [9] 0 0
Baseline to Month 7

Eligibility
Key inclusion criteria
* Male or female, = 18 years of age (19 years or older in South Korea)
* Current diagnosis of Mycobacterium avium Complex (MAC) lung infection
* Positive sputum culture for MAC within 6 months prior to screening
* A chest computed 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
* Ability to produce (spontaneously or with induction) approximately 2 mL of sputum for mycobacteriology at Screening
* Women of child-bearing potential (WOCBP) (ie, fertile following menarche and until becoming post-menopausal 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 while participating in the study
* 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 amikacin liposome inhalation suspension (ALIS) (including clinical study)
* Known hypersensitivity or contraindications to use to ALIS, aminoglycosides, or any of their excipients
* Disseminated MAC infection
* Positive pregnancy test or lactation at Screening. All WOCBP will be tested. Women not of childbearing potential are defined as postmenopausal (ie, amenorrheic for 12 months without an alternative medical cause or confirmed by more than one follicle stimulating hormone [FSH] measurement), or naturally or surgically sterile through bilateral oophorectomy, hysterectomy, or bilateral salpingectomy. For women under the age of 45 years, confirmatory testing with FSH should be considered
* Administration of any investigational drug within 8 weeks prior to Screening
* Known or suspected acquired immunodeficiency syndromes (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
* MAC isolate with MIC for clarithromycin = 32 µg/mL at Screening
* 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
Other
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 administering the treatment/s
The people assessing the outcomes
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
AUS010 - Chermside
Recruitment hospital [2] 0 0
AUS011 - Woolloongabba
Recruitment hospital [3] 0 0
AUS008 - Adelaide
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
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
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Argentina
State/province [17] 0 0
Córdoba
Country [18] 0 0
Austria
State/province [18] 0 0
Linz
Country [19] 0 0
Denmark
State/province [19] 0 0
Zeeland
Country [20] 0 0
Denmark
State/province [20] 0 0
Aalborg
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Hessen
Country [24] 0 0
Germany
State/province [24] 0 0
Niedersachsen
Country [25] 0 0
Germany
State/province [25] 0 0
Nordrhein-Westfalen
Country [26] 0 0
Germany
State/province [26] 0 0
Dresden
Country [27] 0 0
Israel
State/province [27] 0 0
Ashkelon
Country [28] 0 0
Israel
State/province [28] 0 0
Haifa
Country [29] 0 0
Israel
State/province [29] 0 0
Petah Tikva
Country [30] 0 0
Israel
State/province [30] 0 0
Ramat Gan
Country [31] 0 0
Italy
State/province [31] 0 0
Emilia-Romagna
Country [32] 0 0
Italy
State/province [32] 0 0
Lazio
Country [33] 0 0
Italy
State/province [33] 0 0
Toscana
Country [34] 0 0
Italy
State/province [34] 0 0
Milan
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seongnam
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
New Zealand
State/province [37] 0 0
Hawkes's Bay
Country [38] 0 0
New Zealand
State/province [38] 0 0
Waikato
Country [39] 0 0
New Zealand
State/province [39] 0 0
Christchurch
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Girona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Taiwan
State/province [43] 0 0
Chiayi
Country [44] 0 0
Taiwan
State/province [44] 0 0
Kaohsiung
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei city

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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?

Results publications and other study-related documents

No documents have been uploaded by study researchers.