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

• Sponsor: Insmed Incorporated (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04677543
• Collaborator: (none)
• Enrollment: 100
• Locations: 134
• Arms: 2
• Anticipated Duration (Months): 30.2
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Infections, Nontuberculous	Drug: ALIS; Drug: Azithromycin; Drug: Ethambutol; Drug: ELC	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Dec 22, 2020
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: ALIS; Inhalation via nebulization over approximately 6 to 15 minutes.; Other Names: Amikacin liposome inhalation suspension ARIKAYCE® ; Drug: Azithromycin; Oral tablet; Other Names: AZI ; Drug: Ethambutol; Oral tablet; Other Names: ETH
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.	Drug: Azithromycin; Oral tablet; Other Names: AZI ; Drug: Ethambutol; Oral tablet; Other Names: ETH ; Drug: ELC; Inhalation via nebulization over approximately 6 to 15 minutes.; Other Names: Empty liposome control

Outcome Measures

Primary Outcome Measures

1. Psychometric Cross-Sectional Validation of Patient Reported Outcome (PRO): Patient Global Impression of Severity (PGI-S) [Baseline]

2. Psychometric Cross-Sectional Validation of PRO: Quality of Life Questionnaire - Bronchiectasis (QoL-B) [Baseline]

3. Psychometric Cross-Sectional Validation of PRO: Patient-Reported Outcome Measurement Information System - Fatigue-Short Form 7a (PROMIS F-SF 7a) [Baseline]

4. 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]

5. 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]

6. 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]

7. 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 Outcome Measures

1. Percentage of Participants Achieving Culture Conversion by Month 6 [Month 6]

2. Change from Baseline in Respiratory Symptom Score at Month 7 [Baseline to Month 7]

3. Change from Baseline in Fatigue Symptom Score at Month 7 [Baseline to Month 7]

4. Time to Culture Conversion [Baseline to Month 6]

5. Time to First Negative Culture [Baseline to Month 6]

6. 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]

7. 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]

8. 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]

9. Number of Participants Who Experience an Adverse Event (AEs) [Baseline to Month 7]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USA008	Birmingham	Alabama	United States	35233-1711
2	USA062	Fresno	California	United States	93701-2302
3	USA060	Los Angeles	California	United States	90033-5320
4	USA058	Sacramento	California	United States	95817
5	USA048	San Diego	California	United States	92121-3018
6	USA055	Santa Barbara	California	United States	93105
7	USA050	Stanford	California	United States	94305
8	USA001	Denver	Colorado	United States	80206
9	USA023	Washington	District of Columbia	United States	20007
10	USA003	Clearwater	Florida	United States	33765
11	USA043	Jacksonville	Florida	United States	32204
12	USA072	Jacksonville	Florida	United States	32207-8202
13	USA047	Jacksonville	Florida	United States	32224
14	USA042	Kissimmee	Florida	United States	34746
15	USA019	Leesburg	Florida	United States	34748
16	USA039	Naples	Florida	United States	34102-5444
17	USA046	New Port Richey	Florida	United States	34652
18	USA014	Saint Petersburg	Florida	United States	33707
19	USA054	Sarasota	Florida	United States	34239
20	USA067	Tampa	Florida	United States	33606-3603
21	USA068	Tampa	Florida	United States	33614
22	USA053	Weston	Florida	United States	33331
23	USA038	Atlanta	Georgia	United States	30342-2147
24	USA066	Augusta	Georgia	United States	30912-0004
25	USA004	Lawrenceville	Georgia	United States	30046-3325
26	USA029	Rincon	Georgia	United States	31326
27	USA031	Chicago	Illinois	United States	60611
28	USA073	Springfield	Illinois	United States	62702-3757
29	USA074	Iowa City	Iowa	United States	52242-1081
30	USA037	Kansas City	Kansas	United States	66160
31	USA002	New Orleans	Louisiana	United States	70112-1393
32	USA017	Baltimore	Maryland	United States	21224-3057
33	USA013	Rochester	Minnesota	United States	55905
34	USA061	Saint Louis	Missouri	United States	63110-1035
35	USA045	Omaha	Nebraska	United States	68124
36	USA069	Hillsborough	New Jersey	United States	08844-1528
37	USA065	Bayside	New York	United States	11361
38	USA011	New York	New York	United States	10017-6739
39	USA076	Charlotte	North Carolina	United States	28204
40	USA051	Durham	North Carolina	United States	27710
41	USA007	Winston-Salem	North Carolina	United States	27103
42	USA064	Cincinnati	Ohio	United States	45267-2800
43	USA018	Cleveland	Ohio	United States	44195
44	USA075	Montgomery	Ohio	United States	45242-5223
45	USA071	Portland	Oregon	United States	97213-2982
46	USA025	Portland	Oregon	United States	97239
47	USA015	DuBois	Pennsylvania	United States	15801
48	USA040	Philadelphia	Pennsylvania	United States	19104-4238
49	USA044	Anderson	South Carolina	United States	29621
50	USA024	Charleston	South Carolina	United States	29414
51	USA020	Charleston	South Carolina	United States	29425
52	USA012	Rock Hill	South Carolina	United States	29732
53	USA022	Franklin	Tennessee	United States	37067
54	USA041	Hendersonville	Tennessee	United States	37075
55	USA021	McKinney	Texas	United States	75069
56	USA006	San Antonio	Texas	United States	78258
57	USA052	Tyler	Texas	United States	75708
58	USA005	Milwaukee	Wisconsin	United States	53226
59	ARG006	Florencio Varela	Buenos Aires	Argentina	B1853AIK
60	ARG005	Quilmes	Buenos Aires	Argentina	B1878FNR
61	ARG004	Buenos Aires	Ciudad Autónoma De BuenosAires	Argentina	C1426ABP
62	ARG002	Cordoba	Córdoba	Argentina	5000
63	ARG001	Rosario	Santa Fe	Argentina	S2000DTC
64	ARG003	Córdoba		Argentina	X5003DCE
65	AUS006	Concord	New South Wales	Australia	2139
66	AUS004	New Lambton	New South Wales	Australia	2305
67	AUS002	Westmead	New South Wales	Australia	2145
68	AUS010	Chermside	Queensland	Australia	4032
69	AUS011	Woolloongabba	Queensland	Australia	4102
70	AUS008	Adelaide	South Australia	Australia	5000
71	AUS007	Clayton	Victoria	Australia	3168
72	AUS005	Perth		Australia	5000
73	AUT001	Linz		Austria	4040
74	CAN003	Winnepeg	Manitoba	Canada	R2H 2A6
75	CAN004	Windsor	Ontario	Canada	N8X-5A6
76	CAN002	Toronto		Canada	M5T 2S8
77	CHL001	Curico	Maule	Chile	3440000
78	CHL002	Quillota		Chile	2260000
79	CHL004	Talca		Chile
80	CHL003	Valparaíso		Chile	2340000
81	DNK001	Roskilde	Zeeland	Denmark	4000
82	DNK004	Aalborg		Denmark	DK-9000
83	DNK002	Aarhus		Denmark	DK-8200
84	DNK003	Odensa C		Denmark	5000
85	GER013	Gauting	Bayern	Germany	82131
86	GER005	München	Bayern	Germany	80335
87	GER002	Frankfurt am Main	Hessen	Germany	60590
88	GER010	Immenhausen	Hessen	Germany	34376
89	GER007	Hannover	Niedersachsen	Germany	30625
90	GER011	Köln	Nordrhein-Westfalen	Germany	51109
91	GER008	Berlin		Germany	13125
92	GER006	Dresden		Germany	01307
93	GER009	Essen		Germany	45127
94	GER004	Freiburg		Germany	79106
95	GRC002	Athens	Attiki	Greece	11527
96	GRC001	Herakleion		Greece	71110
97	HUN002	Budapest		Hungary	1121
98	ISR001	Ashkelon		Israel	78100
99	ISR007	Haifa		Israel	34362
100	ISR003	Petah Tikva		Israel	4910000
101	ISR004	Ramat Gan		Israel	52621
102	ITA006	Modena	Emilia-Romagna	Italy	41100
103	ITA005	Roma	Lazio	Italy	00168
104	ITA008	Siena	Toscana	Italy	53100
105	ITA004	Firenze		Italy	50134
106	ITA001	Milano		Italy	20122
107	ITA009	Milano		Italy	20123
108	ITA002	Milan		Italy	20162
109	KOR005	Seongnam	Gyeonggido	Korea, Republic of	13620
110	KOR004	Seoul		Korea, Republic of	03722
111	KOR002	Seoul		Korea, Republic of	05505
112	KOR003	Seoul		Korea, Republic of	06973
113	NLD001	Groesbeek		Netherlands	6561 KE
114	NZL002	Hamilton	Waikato	New Zealand	3204
115	NZL004	Auckland		New Zealand	1051
116	NZL001	Christchurch		New Zealand	8461
117	NZL003	Havelock North		New Zealand	4130
118	POL003	Kielce	Swietokrzyskie	Poland	25-751
119	ESP007	Vigo	Pontevedra	Spain	36312
120	ESP002	Barcelona		Spain	08003
121	ESP003	Barcelona		Spain	8035
122	ESP005	Girona		Spain	17007
123	ESP001	Madrid		Spain	28034
124	ESP004	Madrid		Spain	28046
125	ESP006	Pontevedra		Spain	36001
126	TWN004	Putzu	Chiayi	Taiwan	61383
127	TWN001	Douliu		Taiwan	640
128	TWN005	Kaohsiung		Taiwan	807
129	TWN003	Kaohsiung		Taiwan	813
130	TWN007	New Taipei City		Taiwan	23561
131	TWN002	Taipei city		Taiwan	116
132	TWN006	Taipei		Taiwan	10002
133	TUR003	Izmir		Turkey	35110
134	TUR002	Kocaeli		Turkey	41380

Sponsors and Collaborators

• Insmed Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Insmed Incorporated
• ClinicalTrials.gov Identifier: NCT04677543
• Other Study ID Numbers: INS-415; 2020-002545-42
• First Posted: Dec 21, 2020
• Last Update Posted: Aug 17, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Insmed Incorporated: Nontuberculous Mycobacterial Lung Infection; Mycobacterium avium complex; Psychometric validation; Patient-reported outcome
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Azithromycin; Amikacin; Ethambutol

Study Results

No Results Posted as of Aug 17, 2022