Tolerability and Safety of Nintedanib in Myositis Associated Interstitial Lung Disease: a Pilot Study

Study Overview
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Brief Summary
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There is likely a role for using anti-fibrotic medications in patients with myositis-associated interstitial lung disease (MA-ILD) to slow down disease progression, especially in patients who have fibrotic and progressive disease. These patients however are currently being excluded from clinical trials of anti-fibrotic agents in progressive ILD because of the concomitant use of immunosuppression. The benefit of anti-fibrotic agents is being assessed in other rheumatic diseases and should be assessed in MA-ILD as well. They are a unique group of patients with a heterogeneous disease, and are much more frequently on concomitant immune-modulating therapy. As such, they should be studied on their own in separate clinical trials, and the use of nintedanib should be studied as an addition to standard of care immunosuppression. The objective of this study is to assess safety and tolerability of nintedanib in patients with MA-ILD.

Official Title
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Tolerability and Safety of Nintedanib in Myositis Associated Interstitial Lung Disease: a Pilot Study

Conditions
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Interstitial Lung Disease, Myopathy, Inflammatory

Intervention / Treatment
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* Drug: Nintedanib 150 milligrams [Ofev]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 18 years and older 2. Diagnosis of autoimmune myopathy (dermatomyositis, polymyositis, overlap myositis or anti-synthetase syndrome) as diagnosed by a rheumatologist. 3. Interstitial lung disease confirmed by high resolution CT scan (Extent of disease 10% or more on CT done within 12 months of enrolment) with evidence of fibrosis, defined as reticular abnormality with traction bronchiectasis with or without honeycombing. 4. Evidence of progressive disease within 24 months of screening visit: Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of >=10% Marginal decline in FVC % pred based on a relative decline of .>=5-<10% combined with worsening of respiratory symptoms Marginal decline in FVC % pred based on a relative decline of >=5-<10% combined with increasing extent of fibrotic changes on chest imaging Worsening of respiratory symptoms such as cough or shortness of breath as well as increasing extent of fibrotic changes on chest imaging as per radiologist or pulmonologist who read the scan 5. Current and ongoing treatment with immunosuppressive medications, on a stable medication regimen and dosage for at least 6 weeks (considered standard of care medical therapy) Concomitant medications allowed are: mycophenolate, azathioprine, tacrolimus, cyclosporine, rituximab (injection within the last year), prednisone low dose =<20 mg daily, Intravenous immunoglobulins Exclusion Criteria: Contraindication to treatment with nintedanib (based on Canadian labeling) The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding. The male patient plans to father a child during the course of the study Hypersensitivity to nintedanib, peanut or soy Elevated liver enzymes greater than 1.5 times the upper limit of normal Creatinine clearance <30 mL/min Patient with risks factors of aneurysm or artery dissection, such as known history of aneurysm or uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group, open label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nintedanib treatment<br>Single arm treatment with nintedanib | Drug: Nintedanib 150 milligrams [Ofev]<br>* All patients will be given nintedanib 150 milligrams orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability - completed doses | Percentage of subjects who complete 24 weeks on nintedanib. Subjects will be considered to have completed the 24 weeks of the study if they took 90% of the study drug doses. | 24 weeks | 
| Safety and adverse events | numbers of patients with adverse events during course of the study | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forced vital capacity |  | 24 weeks | 
| Change in diffusion capacity of the lung for carbon monoxide |  | 24 weeks | 
| Change in 6 minute walking distance |  | 24 weeks |