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

Mycobacterium Infections, Nontuberculous Clinical Trial

— ARISE  

Official 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 Avi

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04677543
• Other study ID #: INS-415
• Secondary ID: 2020-002545-42
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2020
• Est. completion date: May 9, 2023

Study information

• Verified date: June 2023
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: May 9, 2023
• Est. primary completion date: May 9, 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)

• 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.

Related Conditions & MeSH terms

• Communicable Diseases
• 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
Inhalation via nebulization over approximately 6 to 15 minutes.

Locations

Country	Name	City	State
Argentina	ARG004	Buenos Aires
Argentina	ARG002	Cordoba	Córdoba
Argentina	ARG003	Córdoba
Argentina	ARG005	Quilmes	Buenos Aires
Argentina	ARG001	Rosario	Santa Fe
Argentina	ARG006	Villa Vatteone	Buenos Aires
Australia	AUS008	Adelaide	South Australia
Australia	AUS010	Chermside	Queensland
Australia	AUS006	Concord	New South Wales
Australia	AUS004	New Lambton	New South Wales
Australia	AUS005	Perth
Australia	AUS002	Westmead	New South Wales
Australia	AUS011	Woolloongabba	Queensland
Austria	AUT001	Linz
Canada	CAN004	Windsor	Ontario
Chile	CHL001	Curico	Maule
Chile	CHL002	Quillota
Chile	CHL003	Valparaíso
Denmark	DNK004	Aalborg
Denmark	DNK002	Aarhus
Denmark	DNK003	Odensa C
Denmark	DNK001	Roskilde	Zeeland
Germany	GER006	Dresden
Germany	GER007	Hannover	Niedersachsen
Germany	GER010	Immenhausen	Hessen
Germany	GER011	Köln	Nordrhein-Westfalen
Germany	GER005	München	Bayern
Israel	ISR001	Ashkelon
Israel	ISR007	Haifa
Israel	ISR003	Petah Tikva
Israel	ISR004	Ramat Gan
Italy	ITA002	Milan
Italy	ITA006	Modena	Emilia-Romagna
Italy	ITA005	Roma	Lazio
Italy	ITA008	Siena	Toscana
Korea, Republic of	KOR005	Seongnam
Korea, Republic of	KOR002	Seoul
Korea, Republic of	KOR003	Seoul
Korea, Republic of	KOR004	Seoul
New Zealand	NZL001	Christchurch
New Zealand	NZL002	Hamilton	Waikato
New Zealand	NZL003	Hastings	Hawkes's Bay
Spain	ESP002	Barcelona
Spain	ESP003	Barcelona
Spain	ESP005	Girona
Spain	ESP001	Madrid
Spain	ESP004	Madrid
Spain	ESP007	Vigo	Pontevedra
Taiwan	TWN004	Chiayi
Taiwan	TWN003	Kaohsiung
Taiwan	TWN005	Kaohsiung
Taiwan	TWN002	Taipei city
United States	USA044	Anderson	South Carolina
United States	USA066	Augusta	Georgia
United States	USA017	Baltimore	Maryland
United States	USA065	Bayside	New York
United States	USA008	Birmingham	Alabama
United States	USA020	Charleston	South Carolina
United States	USA024	Charleston	South Carolina
United States	USA064	Cincinnati	Ohio
United States	USA003	Clearwater	Florida
United States	USA018	Cleveland	Ohio
United States	USA001	Denver	Colorado
United States	USA051	Durham	North Carolina
United States	USA022	Franklin	Tennessee
United States	USA062	Fresno	California
United States	USA041	Hendersonville	Tennessee
United States	USA069	Hillsborough	New Jersey
United States	USA072	Jacksonville	Florida
United States	USA037	Kansas City	Kansas
United States	USA042	Kissimmee	Florida
United States	USA021	McKinney	Texas
United States	USA039	Naples	Florida
United States	USA046	New Port Richey	Florida
United States	USA011	New York	New York
United States	USA040	Philadelphia	Pennsylvania
United States	USA025	Portland	Oregon
United States	USA029	Rincon	Georgia
United States	USA012	Rock Hill	South Carolina
United States	USA061	Saint Louis	Missouri
United States	USA014	Saint Petersburg	Florida
United States	USA048	San Diego	California
United States	USA050	Stanford	California
United States	USA067	Tampa	Florida
United States	USA052	Tyler	Texas
United States	USA023	Washington	District of Columbia
United States	USA007	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Canada,  Chile,  Denmark,  Germany,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psychometric Cross-Sectional Validation of Patient Reported Outcome (PRO): Patient Global Impression of Severity (PGI-S)		Baseline
Primary	Psychometric Cross-Sectional Validation of PRO: Quality of Life Questionnaire - Bronchiectasis (QoL-B)		Baseline
Primary	Psychometric Cross-Sectional Validation of PRO: Patient-Reported Outcome Measurement Information System - Fatigue-Short Form 7a (PROMIS F-SF 7a)		Baseline
Primary	Assessment of Test-Retest Reliability Reported as the Estimate of Score Among Participants Reporting no Change on Respiratory PGI-S Applied to QOL-B Respiratory Domain Between Screening and Baseline		Screening (Day -70 to Day 1) and Baseline
Primary	Assessment of Test-Retest Reliability Reported as the Estimate of Score Among Participants Reporting no Change on Fatigue PGI-S Applied to PROMIS F-SF 7a Between Screening and Baseline		Screening (Day -70 to Day 1) and Baseline
Primary	Response Rate as Assessed by Within-Participant Meaningful Change Estimated via Anchor-Based Methods and Validated via Empirical Cumulative Distribution Functions (eCDFs)		Baseline to Month 7
Primary	Response Rate as Assessed by Within-Participant Meaningful Change Estimated via Anchor-Based Methods and Validated via Empirical Probability Density Functions (ePDFs)		Baseline to Month 7
Secondary	Percentage of Participants Achieving Culture Conversion by Month 6		Month 6
Secondary	Change from Baseline in Respiratory Symptom Score at Month 7		Baseline to Month 7
Secondary	Change from Baseline in Fatigue Symptom Score at Month 7		Baseline to Month 7
Secondary	Time to Culture Conversion		Baseline to Month 6
Secondary	Time to First Negative Culture		Baseline to Month 6
Secondary	Percentage of Participants Who Develop a Mycobacterium avium Complex (MAC) Isolate With Amikacin Minimum Inhibitory Concentration (MIC) = 128 micrograms per millliliter (µg/mL) at More Than 1 Visit		Up to Month 7
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 7
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 7
Secondary	Number of Participants Who Experience an Adverse Event (AEs)		Baseline to Month 7