Clinical trial NCT04677543: Validation of Patient Reported Outcome Measures in Participants With Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex
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 Avium Complex (MAC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mycobacterium Infections, Nontuberculous
Keywords: Nontuberculous Mycobacterial Lung Infection
Mycobacterium avium complex
Psychometric validation
Patient-reported outcome
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Psychometric Cross-Sectional Validation of Patient Reported Outcome (PRO): Patient Global Impression of Severity (PGI-S) Respiratory Scale Score at Baseline
timeFrame: Baseline
measure: Psychometric Cross-Sectional Validation of PRO: PGI-S Fatigue Scale Score at Baseline
timeFrame: Baseline
measure: Psychometric Cross-Sectional Validation of PRO: Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms Scale Score at Baseline
timeFrame: Baseline
measure: Psychometric Cross-Sectional Validation of PRO: Patient-Reported Outcome Measurement Information System - Fatigue-Short Form 7a (PROMIS F-SF 7a) Score at Baseline
timeFrame: Baseline
measure: 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
timeFrame: From Screening to Baseline (Day -70 to Day 1)
measure: 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
timeFrame: From Screening to Baseline (Day -70 to Day 1)
measure: 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)
timeFrame: Baseline to Month 7
measure: Response Rate as Assessed by WSMC for PROMIS Fatigue Final Score Estimated Via Anchor-Based Methods and Validated Via eCDFs
timeFrame: Baseline to Month 7
Secondary outcomes:
measure: Percentage of Participants Achieving Culture Conversion by Month 6
timeFrame: Baseline to Month 6
measure: Change From Baseline in QOL-B Respiratory Symptom Score at Month 7
timeFrame: Baseline to Month 7
measure: Change From Baseline in PROMIS F-SF 7a Score at Month 7
timeFrame: Baseline to Month 7
measure: Time to First Culture Conversion
timeFrame: Baseline to Month 6
measure: Time to First Negative Culture
timeFrame: Baseline to Month 7
measure: 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
timeFrame: Up to Month 7
measure: 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
timeFrame: Baseline to Month 7
measure: 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
timeFrame: Baseline to Month 7
measure: Number of Participants Who Experience Any Treatment-emergent Adverse Event (TEAE)
timeFrame: Baseline to Month 7
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: USA008
state: Alabama
city: Fresno
country: United States
facility: USA062
state: California
city: San Diego
country: United States
facility: USA048
state: California
city: Stanford
country: United States
facility: USA050
state: California
city: Washington
country: United States
facility: USA023
state: District of Columbia
city: Clearwater
country: United States
facility: USA003
state: Florida
city: Jacksonville
country: United States
facility: USA072
state: Florida
city: Kissimmee
country: United States
facility: USA042
state: Florida
city: Naples
country: United States
facility: USA039
state: Florida
city: Saint Petersburg
country: United States
facility: USA014
state: Florida
city: Tampa
country: United States
facility: USA067
state: Florida
city: Augusta
country: United States
facility: USA066
state: Georgia
city: Rincon
country: United States
facility: USA029
state: Georgia
city: Kansas City
country: United States
facility: USA037
state: Kansas
city: Baltimore
country: United States
facility: USA017
state: Maryland
city: Saint Louis
country: United States
facility: USA061
state: Missouri
city: Hillsborough
country: United States
facility: USA069
state: New Jersey
city: Bayside
country: United States
facility: USA065
state: New York
city: New York
country: United States
facility: USA011
state: New York
city: Durham
country: United States
facility: USA051
state: North Carolina
city: Portland
country: United States
facility: USA025
state: Oregon
city: Philadelphia
country: United States
facility: USA040
state: Pennsylvania
city: Anderson
country: United States
facility: USA044
state: South Carolina
city: Charleston
country: United States
facility: USA024
state: South Carolina
city: Franklin
country: United States
facility: USA022
state: Tennessee
city: McKinney
country: United States
facility: USA021
state: Texas
city: Tyler
country: United States
facility: USA052
state: Texas
city: Córdoba
country: Argentina
facility: ARG003
city: Chermside
country: Australia
facility: AUS010
state: Queensland
city: Woolloongabba
country: Australia
facility: AUS011
state: Queensland
city: Adelaide
country: Australia
facility: AUS008
state: South Australia
city: Linz
country: Austria
facility: AUT001
city: Roskilde
country: Denmark
facility: DNK001
state: Zeeland
city: Aalborg
country: Denmark
facility: DNK004
city: Aarhus
country: Denmark
facility: DNK002
city: München
country: Germany
facility: GER005
state: Bayern
city: Immenhausen
country: Germany
facility: GER010
state: Hessen
city: Hannover
country: Germany
facility: GER007
state: Niedersachsen
city: Köln
country: Germany
facility: GER011
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GER006
city: Ashkelon
country: Israel
facility: ISR001
city: Haifa
country: Israel
facility: ISR007
city: Petah Tikva
country: Israel
facility: ISR003
city: Ramat Gan
country: Israel
facility: ISR004
city: Modena
country: Italy
facility: ITA006
state: Emilia-Romagna
city: Roma
country: Italy
facility: ITA005
state: Lazio
city: Siena
country: Italy
facility: ITA008
state: Toscana
city: Milan
country: Italy
facility: ITA002
city: Seongnam
country: Korea, Republic of
facility: KOR005
city: Seoul
country: Korea, Republic of
facility: KOR002
city: Seoul
country: Korea, Republic of
facility: KOR003
city: Hastings
country: New Zealand
facility: NZL003
state: Hawkes's Bay
city: Hamilton
country: New Zealand
facility: NZL002
state: Waikato
city: Christchurch
country: New Zealand
facility: NZL001
city: Barcelona
country: Spain
facility: ESP002
city: Barcelona
country: Spain
facility: ESP003
city: Girona
country: Spain
facility: ESP005
city: Madrid
country: Spain
facility: ESP001
city: Madrid
country: Spain
facility: ESP004
city: Chiayi
country: Taiwan
facility: TWN004
city: Kaohsiung
country: Taiwan
facility: TWN005
city: Taipei city
country: Taiwan
facility: TWN002
Study officials:
References: