Validation of Patient Reported Outcome Measures in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex

NCT ID: NCT04677543

Last Updated: 2024-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2023-05-09

Brief Summary

The primary objective of this study is to generate evidence demonstrating the domain specification (via modern psychometric methods), reliability, validity, and responsiveness (within-subject meaningful change) of the Patient-Reported Outcome (PRO) endpoints.

Detailed Description

Participants will also complete the EXAcerbations of Chronic Pulmonary Disease Tool (EXACT), EXACT Respiratory Symptoms (EXACT-RS), St. George Respiratory Questionnaire (SGRQ), Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Patient Global Impression of Severity - Respiratory (PGIS-Respiratory), and Patient Global Impression of Severity - Fatigue (PGIS-Fatigue) at baseline and throughout the study as anchors for the validation of the QoL-B and PROMIS F-SF 7a.

Conditions

Mycobacterium Infections, Nontuberculous

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

ALIS

Intervention Type: DRUG

Inhalation via nebulization over approximately 6 to 15 minutes.

Azithromycin

Intervention Type: DRUG

Oral tablet

Ethambutol

Intervention Type: DRUG

Oral tablet

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.

Group Type: PLACEBO_COMPARATOR

Azithromycin

Intervention Type: DRUG

Oral tablet

Ethambutol

Intervention Type: DRUG

Oral tablet

ELC

Intervention Type: DRUG

Inhalation via nebulization over approximately 6 to 15 minutes.

Interventions

ALIS

Inhalation via nebulization over approximately 6 to 15 minutes.

Intervention Type: DRUG

Azithromycin

Oral tablet

Intervention Type: DRUG

Ethambutol

Oral tablet

Intervention Type: DRUG

ELC

Inhalation via nebulization over approximately 6 to 15 minutes.

Intervention Type: DRUG

Other Intervention Names

Amikacin liposome inhalation suspension; ARIKAYCE®; AZI; ETH; Empty liposome control

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insmed Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

USA008

Birmingham, Alabama, United States

USA062

Fresno, California, United States

USA048

San Diego, California, United States

USA050

Stanford, California, United States

USA023

Washington D.C., District of Columbia, United States

USA003

Clearwater, Florida, United States

USA072

Jacksonville, Florida, United States

USA042

Kissimmee, Florida, United States

USA039

Naples, Florida, United States

USA014

St. Petersburg, Florida, United States

USA067

Tampa, Florida, United States

USA066

Augusta, Georgia, United States

USA029

Rincon, Georgia, United States

USA037

Kansas City, Kansas, United States

USA017

Baltimore, Maryland, United States

USA061

St Louis, Missouri, United States

USA069

Hillsborough, New Jersey, United States

USA065

Bayside, New York, United States

USA011

New York, New York, United States

USA051

Durham, North Carolina, United States

USA025

Portland, Oregon, United States

USA040

Philadelphia, Pennsylvania, United States

USA044

Anderson, South Carolina, United States

USA024

Charleston, South Carolina, United States

USA022

Franklin, Tennessee, United States

USA021

McKinney, Texas, United States

USA052

Tyler, Texas, United States

ARG003

Córdoba, , Argentina

AUS010

Chermside, Queensland, Australia

AUS011

Woolloongabba, Queensland, Australia

AUS008

Adelaide, South Australia, Australia

AUT001

Linz, , Austria

DNK001

Roskilde, Zeeland, Denmark

DNK004

Aalborg, , Denmark

DNK002

Aarhus, , Denmark

GER005

München, Bavaria, Germany

GER010

Immenhausen, Hesse, Germany

GER007

Hanover, Lower Saxony, Germany

GER011

Cologne, North Rhine-Westphalia, Germany

GER006

Dresden, , Germany

ISR001

Ashkelon, , Israel

ISR007

Haifa, , Israel

ISR003

Petah Tikva, , Israel

ISR004

Ramat Gan, , Israel

ITA006

Modena, Emilia-Romagna, Italy

ITA005

Rome, Lazio, Italy

ITA008

Siena, Tuscany, Italy

ITA002

Milan, , Italy

NZL003

Hastings, Hawkes's Bay, New Zealand

NZL002

Hamilton, Waikato Region, New Zealand

NZL001

Christchurch, , New Zealand

KOR005

Seongnam, , South Korea

KOR002

Seoul, , South Korea

KOR003

Seoul, , South Korea

ESP002

Barcelona, , Spain

ESP003

Barcelona, , Spain

ESP005

Girona, , Spain

ESP001

Madrid, , Spain

ESP004

Madrid, , Spain

TWN004

Chiayi City, Chiayi, Taiwan

TWN005

Kaohsiung City, , Taiwan

TWN002

Taipei, , Taiwan

Countries

United States; Argentina; Australia; Austria; Denmark; Germany; Israel; Italy; New Zealand; South Korea; Spain; Taiwan

References

Daley CL, Chalmers JD, Flume PA, Griffith DE, Hasegawa N, Morimoto K, Winthrop KL, Sheu CC, Avsar K, Andrisani D, Codecasa LR, Yuen DW, Hassan M, Nevoret ML, Mange K. Trial Conduct, Baseline Characteristics, and Symptom Burden of Patients in the ARISE Study. Pulm Ther. 2025 Jun;11(2):269-283. doi: 10.1007/s41030-025-00293-3. Epub 2025 Apr 8.

Reference Type: DERIVED

PMID: 40198465 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-002545-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INS-415

Identifier Type: -

Identifier Source: org_study_id