Myositis Interstitial Lung Disease Nintedanib Trial

Exclusion Criteria

• •1. Planned major surgical procedures within the trial period of 24 weeks.
• •2. Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• •3. Women of childbearing potential\* not willing or able to use at least two highly effective methods of birth control.
• •1. 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.
• •2. 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.
• •4. Severe lung disease is defined by the following within the last 6 months before the screening:
• •1. FVC ≤40 percent predicted
• •2. DLCO \<30% of percent predicted (corrected for Hb)
• •3. O2 requirement of ≥10 L at rest based on home oxygen prescription.
• •4. Patient listed for lung transplant or actively going through lung transplant evaluation.
• •5. Moderate to severe active muscle disease from myositis as per any one of the criteria:
• •1. Creatine kinase (CK) \> 2000 U/mL.
• •2. Moderate to severe dermatomyositis rashes as per investigator evaluation (if rash present)
• •3. Moderate to severe arthritis as per investigator evaluation
• •4. Moderate to severe muscle weakness as per Sit to Stand 30 seconds of \< 7.
• •6. History of or ongoing serious active, chronic, or recurrent infection within 4 weeks of screening
• •7. Significant Pulmonary Hypertension (PH) is defined by any of the following:
• •1. Current clinical diagnosis of moderate to severe PH or significant right heart failure.
• •2. History of echocardiographic evidence of significant right heart failure or moderate to severe PH (TR jet \>= 2.9 m/s and signs of right ventricle (RV) dysfunction; or TR jet \> 3.4; or an right ventricle systolic pressure (RVSP) \> 40-55 with evidence of RV strain or dysfunction; or RVSP \> 55 regardless.
• •3. History of right heart catheterization showing a cardiac index ≤ 2.2 l/min/m² or severity of pulmonary hypertension (mPAP) \>40 millimeters of mercury (mmHg) with a pulmonary capillary wedge pressure (PCWP) \<15mmHg
• •4. PH requiring oral, IV, or inhaled therapy (such as epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, sildenafil, and tadalafil).
• •8. Increased bleeding risk, defined by any of the following:
• •1. Patients who require
• •* Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, factor Xa inhibitors, low molecular weight heparin)
• •* High dose antiplatelet therapy (\>325mg acetylsalicylic acid or \>75mg clopidogrel).
• •2. History of hemorrhagic central nervous system (CNS) event within 12 months of screening.
• •3. Any of the following within 3 months of screening:
• •* Hemoptysis or hematuria
• •* Active gastrointestinal (GI) bleeding or active GI ulcers.
• •4. Coagulation parameters: International normalized ratio (INR) \>2, prolongation of prothrombin time (PT) and by \>1.5 x ULN at screening.
• •9. History of a thrombotic event (including stroke and transient ischemic attack) within 12 months of screening.
• •10. Severe Cardiovascular disease, any of the following:
• •1. Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 months of screening.
• •2. Myocardial infarction or unstable cardiac angina within 6 months of screening.
• •11. Patients with underlying chronic liver disease (Child-Pugh A, B, or C hepatic impairment).
• •12. Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
• •13. Other diseases that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation (such as significant GI issues like irritable bowel syndrome, inflammatory bowel disease, recent abdominal surgery, diverticular disease), or significant other lung diseases (such as severe obstructive lung disease such as severe asthma or severe chronic obstructive pulmonary disease, etc.) or may put the patient at risk when participating in this trial.
• •14. Life expectancy for a disease other than ILD \< 2.5 years (Investigator assessment).
• •15. In the opinion of the investigator, any condition precluding participation and completion of the study, including active alcohol and drug abuse or patients not able to understand or follow trial procedures.
• •16. Other investigational therapy was received within 1 month or 6 half-lives (whichever was greater) before the screening visit.
• •17. Current treatment with nintedanib or pirfenidone (taken the drug within 3 months of randomization or history of intolerance/side effects)
• •18. Current or recent use of one or more of the following medications (See: SOC immunosuppression and washout under section 6.2 for details)
• •1. Cyclophosphamide within 3 months of baseline.
• •2. Anti-tumor necrosis factor (infliximab, golimumab, or certolizumab) within 8 weeks or adalimumab within 4 weeks, and etanercept within 2 weeks of baseline.
• •3. Anakinra within 1 week of baseline.
• •4. Other biological agents such as tocilizumab, etc. within 4 weeks of baseline.
• •19. Safety laboratory abnormality as any one of below
• •1. Aspartate transferase (AST), alanine aminotransferase (ALT) \> 1.5 x ULN at screening, unless deemed due to active myositis by investigator, in which case CK is also abnormally elevated and the ratio of AST or ALT by CK levels (adjusted as x ULN) should be \< 2.0 and gamma-glutamyl transferase \< 2.0 x ULN.
• •2. Bilirubin \> 1.5 x ULN at screening
• •3. Creatinine clearance \<30 mL/min calculated by Cockcroft-Gault formula at screening.
• •4. Hgb \< 9.0
• •5. Platelet count \< 100,000/mm3
• •6. White blood cells \< 3000/mm3
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