Myositis Interstitial Lung Disease Nintedanib Trial

NCT05799755 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STUDY22090061
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 10

Brief Summary

This research study will evaluate safety and how well the study drug, nintedanib improve symptoms in participants with myositis associated interstitial lung disease (MA-ILD). Interstitial lung disease is a disorder caused by the abnormal accumulation of cells structures between air sacs of the lungs resulting in thickening, stiffness and scarring of the tissues of the lung. This study will enroll a total of 134 participants across 15 clinical sites located in the United States. A subset of participants will be enrolled remotely via telemedicine utilizing certified mobile home research nurses and various remote monitoring devices. The research visits may include a physical exam, vital signs (such as blood pressure, heart rate, etc.), pulmonary function tests (PFT and/or home spirometry), Computerized Tomography (or CT) scans of the chest, blood draws, wearing a physical activity monitor and completing questionnaires. Some of these events may be done at home, at a local facility or remotely (via telemedicine).

Conditions

Myositis Associated Interstitial Lund Disease (MA-ILD)

Keywords

Myositis associated interstitial lung disease (Myositis ILD); Interstitial Lung Disease (ILD); Myositis

Outcome Measures

Primary Outcomes (1)

• Change in Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) Dyspnea score

  The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: 1) dyspnea, 2) cough and 3) fatigue as well as a total Symptoms score. The Impacts module yields a single Impacts score. Symptoms and Impacts scores are summed to yield a total L-PF score. Scoring is performed as a summary score, the mean of the dimension ratings multiplied by 100. Summary score range from 0-100, the higher the score the greater the impairment.

  Baseline (week 0) to 12 weeks

Secondary Outcomes (16)

• Change in Living with Pulmonary Fibrosis Dyspnea score

  Baseline (week 0) to week 24

• Change in other Living with Pulmonary Fibrosis scores

  Week 12 to week 24

• Change in immunosuppressive (IS) regimen

  Baseline (Week 0) to week 12

• Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 12 weeks

  Baseline (week 0) to week 12

• Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 24 weeks

  Baseline (week 0) to week 24

Other Outcomes (19)

• Rate of patient recruitment, enrollment, screen failure, and dropout rates between the local sites (average per site) and the remote site

  Baseline (week 0) to week 24

• Reliability measure of Forced Vital Capacity (FVC) in ml measured by home spirometry

  Baseline (week 0) to week 24

• Validity of Forced Vital Capacity (FVC) in ml by home spirometry

  Baseline (week 0) to week 24

Study Arms (2)

Placebo plus Standard of Care, then Nintedanib plus Standard of Care

PLACEBO COMPARATOR

Placebo twice a day (BID) plus standard of care (SOC) Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.

Drug: Nintedanib; Drug: Placebo; Drug: Standard of Care

Nintedanib plus Standard of Care

ACTIVE COMPARATOR

Nintedanib 150 mg BID + SOC Immunosuppressive Therapy for 12 weeks followed by open-label Nintedanib 150mg BID + SOC Immunosuppressive Therapy for additional 12 weeks.

Drug: Nintedanib; Drug: Standard of Care

Interventions

Nintedanib DRUG

Nintedanib 150 mg BID

Also known as: OFEV

Nintedanib plus Standard of Care; Placebo plus Standard of Care, then Nintedanib plus Standard of Care

Placebo DRUG

Placebo comparator

Placebo plus Standard of Care, then Nintedanib plus Standard of Care

Standard of Care DRUG

Maximum of 2 standard of care immunosuppressant (IS) drugs are allowed, one being a glucocorticoid (GC) and the other being a non-GC IS drug OR 2 non-GC IS drugs in the event that the patient is not on a GC). The patient should be on the IS drug(s) for at least 12 weeks (at least 4 weeks or more for GC) before the screening. The doses should be stable for at least 4 weeks (at least 2 weeks for GC) before the screening visit.

Nintedanib plus Standard of Care; Placebo plus Standard of Care, then Nintedanib plus Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided written informed consent
• Approval from local treating physician (done at pre-screening only for remote patients as well as for local site patients not actively being managed at the local site).
• Subject lives in the United States
• Adult: Age ≥ 18 years
• Subject can speak, read, and understand English or Spanish
• Subject is willing and capable of performing all study procedures.
• Validity/repeatability of home spirometry confirmed by PFT lab technician/MD through telemedicine as per American Thoracic Society guidelines.
• Men and women of reproductive potential must agree to use 2 reliable methods of birth control during the trial period.
• Clinical diagnosis of myositis or presence of one of the following myositis-specific or -associated autoantibodies).
• Anti-synthetase autoantibody (Anti-Jo-1, -PL-7, -PL-12, -EJ, -OJ, -KS, -Tyr, -Zo)
• Anti-MDA5, TIF1-gamma, Mi-2, NXP2/MJ, SAE, HMGCR, SRP
• Anti-PM/Scl, Ku, U1RNP, Ro5,2/60, or SSA (in absence of clinical diagnosis of systemic sclerosis or primary Sjogren syndrome).
• Fibrosing Interstitial Lung Disease (ILD):
• HRCT chest within 12 months of screening visit with fibrosing ILD (reticular changes, traction bronchiectasis, and/or honeycombing)
• No other identifiable cause of fibrosis

You may not qualify if:

• Planned major surgical procedures within the trial period of 24 weeks.
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• Women of childbearing potential\* not willing or able to use at least two highly effective methods of birth control.
• For females of reproductive potential: use of highly effective contraception for at least 1 month before study drug administration and agreement to use such a method during study participation and for an additional 28 days after the end of study drug administration.
• For males of reproductive potential\*\*: use of condoms or other methods to ensure effective contraception with a partner
• Highly effective contraception examples are:
• An approved hormonal contraceptive such as oral contraceptives, emergency contraception used as directed, patches, implants, injections, rings, hormonally-impregnated intrauterine device (IUD), or nonhormonal IUD.
• Abstinence
• Condoms
• A woman is considered of childbearing potential, i.e. fertile, following menarche, and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, tubal occlusion, and bilateral oophorectomy.
• A man is considered permanently sterile if a vasectomy has been performed.
• Severe lung disease is defined by the following within the last 6 months before the screening:
• FVC ≤40 percent predicted
• DLCO \<30% of percent predicted (corrected for Hb)
• O2 requirement of ≥10 L at rest based on home oxygen prescription.

Sponsors & Collaborators

• Rohit Aggarwal, MD: lead
• Boehringer Ingelheim: collaborator

Study Sites (10)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Northwell Health

New York, New York, 11021, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15216, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84112, United States

Location

Related Publications (8)

• Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, Clerisme-Beaty E, Stowasser S, Tetzlaff K, Kuwana M, Maher TM; SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528. doi: 10.1056/NEJMoa1903076. Epub 2019 May 20.

  PMID: 31112379 BACKGROUND

• Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, Coeck C, Clerisme-Beaty E, Rosenstock B, Quaresma M, Haeufel T, Goeldner RG, Schlenker-Herceg R, Brown KK; INBUILD Trial Investigators. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019 Oct 31;381(18):1718-1727. doi: 10.1056/NEJMoa1908681. Epub 2019 Sep 29.

  PMID: 31566307 BACKGROUND

• Wilfong EM, Aggarwal R. Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease. Ther Adv Musculoskelet Dis. 2021 Dec 9;13:1759720X211060907. doi: 10.1177/1759720X211060907. eCollection 2021.

  PMID: 34917177 BACKGROUND

• Shen L, Yan Q, Chen X. Efficacy of Combination Therapy With Pirfenidone and Low-Dose Cyclophosphamide for Refractory Interstitial Lung Disease Associated With Connective Tissue Disease: A Case-Series of Seven Patients. Arch Rheumatol. 2019 Aug 26;35(2):180-188. doi: 10.46497/ArchRheumatol.2020.7381. eCollection 2020 Jun.

  PMID: 32851366 BACKGROUND

• Li T, Guo L, Chen Z, Gu L, Sun F, Tan X, Chen S, Wang X, Ye S. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis. Sci Rep. 2016 Sep 12;6:33226. doi: 10.1038/srep33226.

  PMID: 27615411 BACKGROUND

• Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, Brown K, Flaherty K, Wells AU, Seibold JR, Strand V. Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group. J Rheumatol. 2015 Nov;42(11):2168-71. doi: 10.3899/jrheum.141182. Epub 2015 Mar 1.

  PMID: 25729034 BACKGROUND

• Liang J, Cao H, Yang Y, Ke Y, Yu Y, Sun C, Yue L, Lin J. Efficacy and Tolerability of Nintedanib in Idiopathic-Inflammatory-Myopathy-Related Interstitial Lung Disease: A Pilot Study. Front Med (Lausanne). 2021 Feb 3;8:626953. doi: 10.3389/fmed.2021.626953. eCollection 2021.

  PMID: 33614683 BACKGROUND

• Aggarwal R, Oddis CV, Sullivan DI, Moghadam-Kia S, Saygin D, Kass DJ, Koontz DC, Li P, Conoscenti CS, Olson AL; MINT investigators. Design of a randomised controlled hybrid trial of nintedanib in patients with progressive myositis-associated interstitial lung disease. BMC Pulm Med. 2024 Oct 30;24(1):544. doi: 10.1186/s12890-024-03314-0.

  PMID: 39478532 DERIVED

MeSH Terms

Conditions

Lung Diseases, Interstitial; Myositis

Interventions

nintedanib; Standard of Care

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Rohit Aggarwal, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects, investigators, and everyone involved in trial conduct or analysis or with any other interest in this double-blind trial will remain blinded with regard to the randomized treatment assignments until after the database lock.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Randomization will be 1:1 for nintedanib: placebo and stratified by underlying immunosuppressive therapy (mycophenolate vs. others). All patients must be on the standard of care (SOC) immunosuppression (IS) at screening as per the protocol and should remain on stable doses throughout the trial. After 12 weeks both arms will receive an additional 12 weeks of nintedanib (150 mg twice a day, maximum dose of 300 mg a day) through week 24 (final study visit).

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: April 5, 2023
• Study Start: August 1, 2023
• Primary Completion: March 17, 2025
• Study Completion: December 31, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data requests will not be accepted prior to final publication of the trial.
• Access Criteria: All data requests will require written approval from sponsor and steering committee prior to release of data

Locations

US (10)