MINT: Myositis Interstitial Lung Disease Nintedanib Trial

Sponsor

Rohit Aggarwal, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05799755

Collaborator

Boehringer Ingelheim (Industry)

134

Enrollment

Locations

Arms

Anticipated Duration (Months)

8.9

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myositis Associated Interstitial Lund Disease (MA-ILD)	Drug: Nintedanib Drug: Placebo Drug: Standard of Care	Phase 4

Detailed Description

Participants enrolled in the study will receive either study drug or placebo for 12 weeks plus the participant's normal standard of care medication for the participant's disease. Placebo is an inactive substance that contains no medicine. Following the initial treatment phase, participants will receive the active study drug (nintedanib) for an additional 12-week period.

Nintedanib is a drug that is currently used and has been approved by the Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF), and has been shown to slow the rate of decline in pulmonary function among patients with IPF as well as interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma. In addition, in March 2020, the FDA approved nintedanib oral capsules to treat patients with chronic fibrosing (scarring) interstitial lung diseases (ILD) with a progressive phenotype (trait).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

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).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).

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

Nintedanib Plus Standard of Care Immunosuppression Versus Standard of Care Immunosuppression Alone in Patients With Progressive Fibrotic Myositis Associated - Interstitial Lung Disease: A Randomized, Double-Blind, Exploratory Trial

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo plus Standard of Care, then Nintedanib plus Standard of Care 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 Nintedanib 150 mg BID Other Names: OFEV Drug: Placebo Placebo comparator Drug: Standard of Care 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.
Active Comparator: Nintedanib plus Standard of Care 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 Nintedanib 150 mg BID Other Names: OFEV Drug: Standard of Care 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.

Arm

Intervention/Treatment

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

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

Nintedanib 150 mg BID

Other Names:

OFEV

Drug: Placebo

Placebo comparator

Drug: Standard of Care

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.

Active Comparator: Nintedanib plus Standard of Care

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

Nintedanib 150 mg BID

Other Names:

OFEV

Drug: Standard of Care

Outcome Measures

Primary Outcome Measures

Change in Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) Dyspnea score [Baseline (week 0) to 12 weeks]
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.

Secondary Outcome Measures

Change in Living with Pulmonary Fibrosis Dyspnea score [Baseline (week 0) to week 24]
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.
Change in other Living with Pulmonary Fibrosis scores [Week 12 to week 24]
The Living with Pulmonary Fibrosis questionnaire (L-PF) scores will include total score, symptoms, cough, energy and impacts scores. The score range is from 0-100, the higher the score, the greater the impairment.
Change in immunosuppressive (IS) regimen [Baseline (Week 0) to week 12]
Proportion of patients requiring an increased dose or a change in their glucocorticoid (GC) / immunosuppression (IS) agent for clinical worsening/flare of MA-ILD
Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 12 weeks [Baseline (week 0) to week 12]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml.
Absolute and relative change in Forced Vital Capacity (FVC) (mL) from baseline to 24 weeks [Baseline (week 0) to week 24]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml.
Absolute and relative change in Forced Vital Capacity FVC (%) from baseline to week 12 [Baseline (week 0) to week 12]
FVC (%) is forced vital capacity parameter derived from a pulmonary function study (PFT)as percentage predicted of healthy standards (in %), respectively.
Absolute and relative change in Forced Vital Capacity FVC (%) from baseline to week 24 [Baseline (week 0) to week 24]
FVC (%) is forced vital capacity parameter derived from a pulmonary function study (PFT)as percentage predicted of healthy standards (in %), respectively.
Proportion of patients with a relative decline from baseline in FVC (mL) of ≥10%, ≥7.5%, and ≥ 5% [Weeks 12 and 24]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively.
Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (mL) from baseline to week 12 [baseline (week 0) at week 12]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Percent change is calculated based on change from baseline to a follow up visit.
Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (mL) from baseline to week 24 [baseline (week 0) at week 24]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Percent change is calculated based on change from baseline to a follow up visit.
Time to FVC (mL) improvement and decline from baseline by (≥5%, 7.5%, 10%) [Baseline (week 0) to 24 weeks]
FVC (ml) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Time to designated change is calculated based on change from baseline to a follow up visit and time since baseline.
Time to progression [Baseline (week 0) to week 24]
Defined as either time for event a, b or c Event a. ≥ 10% decline in FVC (mL) or death or transplant Event b. ILD worsening definition (per protocol) or death or transplant Event c. non-elective hospitalization for ILD worsening/flare or death or lung transplant
Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (%) from baseline to week 12 [baseline (week 0) at week 12]
FVC (%) are forced vital capacity parameter derived from a pulmonary
Proportion of patients with stable (+/- < 5%) or improved FVC (≥ 5, ≥ 7.5, ≥ 10%) (%) from baseline to week 24 [baseline (week 0) at week 24]
FVC (%) are forced vital capacity parameter derived from a pulmonary
Proportion of patients with a relative decline from baseline in FVC (%) of ≥10%, ≥7.5%, and ≥ 5% [Weeks 12 and 24]
FVC (%) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively.
Time to FVC (%) improvement and decline from baseline by (≥5%, 7.5%, 10%) [Baseline (week 0) to 24 weeks]
FVC (%) is forced vital capacity parameter derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Time to designated change is calculated based on change from baseline to a follow up visit and time since baseline.

Other Outcome Measures

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]
Compare the patient recruitment, enrollment, screen failure and drop out rates between patient recruited through local clinical trial sites vs. remote clinical trial site.
Reliability measure of Forced Vital Capacity (FVC) in ml measured by home spirometry [Baseline (week 0) to week 24]
Reliability is measured as test (baseline) and re-test (week 1) correlation of FVC in ml using spearman correlation.
Validity of Forced Vital Capacity (FVC) in ml by home spirometry [Baseline (week 0) to week 24]
Validity of FVC (ml) by home spirometry is measured as spearman correlation with FVC (ml) obtained by gold standard clinic spirometry.
Absolute and relative change in DLCO [Baseline (week 0) to week 24]
DLCO is diffusing capacity of the lungs for carbon monoxide (DLCO) derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Changes from baseline to follow up will be calculated and compared between two treatment arms.
Progression free survival [weeks 12 and 24]
Connective Tissue Disease (CTD)-ILD outcome as per Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT), which is defined as the occurrence of any of the following: death or lung transplant or FVC ≥10% decline or FVC ≥5% decline with DLCO ≥15% decline Clinical worsening is defined as death, lung transplant, or new/worsening O2 requirement at rest (>2L), or non-elective hospitalization for ILD clinical worsening/flare or ILD worsening definition (per protocol) or out of protocol rescue medication for ILD clinical worsening/flare.
Steroid use (calculated using prednisone dose equivalents) [Weeks 12 and 24]
Comparing change of steroid from baseline to follow up, between 2 treatment groups
Change in supplemental oxygen needs from baseline to week 12 [Baseline (week 0) to 12 weeks]
Comparing change in oxygen requirement from baseline to follow up, between 2 treatment groups
Mean change in supplemental oxygen requirement in ml from baseline to week 24 [Baseline (week 0) to 24 weeks]
Comparing change in oxygen requirement from baseline to follow up, between 2 treatment groups
Patient assessment of change [Weeks 12 and 24]
Patient Assessment of Change (also known as Patient Global Impression of Change): Overall Assessment of Change by Patient. Patient overall assessment of change in disease status from baseline, reported as 7-point ordinal scale: no change, minimal, moderate, and major worsening as well as minimal, moderate and major improvement.
Physician assessment of change [Weeks 12 and 24]
Physician's overall assessment of change in disease status of the patient from baseline, reported as 7-point ordinal scale: no change, minimal, moderate, and major worsening as well as minimal, moderate and major improvement.
Change in Cadence by Physical Activity Monitor at week 12. [Baseline (week 0) to 12 weeks]
Cadence: highest step counts performed in a minute for a given day. Higher value is better. Mean change in cadence from baseline to week 12.
Change in Average Daily Step Count by Physical Activity Monitor at week 12. [Baseline (week 0) to 12 weeks]
Average daily step count measured by mean of daily step count for 7 days, where daily step counts in a day divided by time the device was worn. Higher value is better. Mean change in average daily step count from baseline to week 12
Change in Cadence by Physical Activity Monitor at week 24. [Baseline (week 0) to 24 weeks]
Cadence: highest step counts performed in a minute for a given day. Higher value is better. Mean change in cadence from baseline to week 24.
Change in Average Daily Step Count by Physical Activity Monitor at week 24. [Baseline (week 0) to 24 weeks]
Average daily step count measured by mean of daily step count for 7 days, where daily step counts in a day divided by time the device was worn. Higher value is better. Mean change in average daily step count from baseline to week 24.
Changes in Sit to Stand test from baseline to week 12 [Baseline (week 0) to 12 weeks]
Evaluate the changes in Sit to Stand test score from baseline to follow up , between two treatment arms
Changes in Sit to Stand test from baseline to week 24 [Baseline (week 0) to 24 weeks]
Evaluate the changes in Sit to Stand test score from baseline to follow up , between two treatment arms
Change in High-Resolution Computed Tomography (HRCT) chest from baseline [Baseline (week 0) to 24 weeks]
Change in HRCT will be analyzed using semi-quantitative and quantitative image based scoring. Change from baseline to follow up will be calculated and compared between two treatment arm
Adverse events (AEs) and tolerance [Baseline (week 0) to week 24]
All AEs and tolerance event will be compared between 2 treatment arms Proportion of subjects who discontinue study drug Patients with any AEs Patients with Serious Adverse Event (SAE)s Patients with AEs of special interest (gastrointestinal perforation and hepatic injury)
Absolute and relative change in FEV1 [Baseline (week 0) to week 24]
FEV1 is forced expiratory volume over 1 second (FEV1) derived from a pulmonary function study (PFT) in volume as ml and as percentage predicted of healthy standards (in %), respectively. Changes from baseline to follow up will be calculated and compared between two treatment arms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Confirmed diagnosis of myositis (2017 American College of Rheumatology/European League Against Rheumatism classification criteria 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
The following co-existing features are expected and accepted: ground glass opacity, upper lung or peri-bronchovascular predominance, mosaic attenuation, air trapping, consolidation, and centrilobular nodules.
Progressive ILD: Defined as meeting ≥1 of the following criteria within 24 months of the screening visit.
≥10% relative decline in FVC% predicted (%pred)
≥5 but <10% relative decline in FVC %pred with worsening dyspnea.
≥5 but <10% relative decline in FVC %pred with worsening chest HRCT fibrotic changes
Worsening dyspnea with worsening chest HRCT fibrosis
The severity of ILD: FVC > 40% of predicted and ≤ 80% of predicted.
Standard of care (SOC) therapy: (See: SOC immunosuppression and washout under section 6.2 for details)
Allowable SOC includes a maximum of 2: 1 glucocorticoid (GC) and 1 Non-GC immunosuppressive medication (IS) Or 2 Non-GC immunosuppressive medications.
Allowable IS component of SOC regimen must have been started at least 12 weeks prior and be stable for at least 4 weeks before screening visit.
Allowable GC component of SOC regimen must have been started at least 4 weeks prior and be stable for at least 2 weeks before screening visit.
Allowable IS and GC:

Glucocorticoid (maximum dose ≤20 mg/day; prednisone equivalent). Mycophenolate mofetil (max dose 3 gm/day) Mycophenolic acid (max dose 1440 mg/day) Azathioprine (max dose 2.5 mg/kg/day) Methotrexate (max dose 25 mg/week Tacrolimus (max dose 10 mg/day) Cyclosporine (max dose 200 mg/day) Leflunomide (max dose 20 mg/day) Sulfasalazine (max dose 3 gm/day) IVIG (Intravenous immunoglobulin) or SQIG (subcutaneous immunoglobulin) (max dose 2 gm/kg/month). Rituximab is allowed if given ≥4 weeks before screening Hydroxychloroquine is allowed and not considered as SOC IS therapy. Inhaled medication(s) for lung disease is allowed if started > 4 weeks before screening.

Should remain stable throughout the study.

Negative pregnancy test

Exclusion Criteria:

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, or hormonally-impregnated intrauterine device (IUD)
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, and bilateral oophorectomy.

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.
Patient listed for lung transplant or actively going through lung transplant evaluation.
Moderate to severe active muscle disease from myositis as per any one of the criteria:
Creatine kinase (CK) > 1000 U/mL.
Moderate to severe dermatomyositis rashes as per investigator evaluation (if rash present)
Moderate to severe arthritis as per investigator evaluation
Moderate to severe muscle weakness as per Sit to Stand 30 seconds of < 7.
History of or ongoing serious active, chronic, or recurrent infection within 4 weeks of screening
Significant Pulmonary Hypertension (PH) is defined by any of the following:
Previous clinical diagnosis of moderate to severe PH or significant right heart failure.
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; TR jet > 3.4; an right ventricle systolic pressure (RVSP) > 40-55 with evidence of RV strain or dysfunction; and RVSP > 55 regardless.
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
PH requiring oral, IV, or inhaled therapy (such as epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, sildenafil, and tadalafil).
Increased bleeding risk, defined by any of the following:
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).

History of hemorrhagic central nervous system (CNS) event within 12 months of screening.
Any of the following within 3 months of screening:

Hemoptysis or hematuria
Active gastrointestinal (GI) bleeding or active GI ulcers.

Coagulation parameters: International normalized ratio (INR) >2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN at screening.
History of a thrombotic event (including stroke and transient ischemic attack) within 12 months of screening.
Severe Cardiovascular disease, any of the following:
Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 months of screening.
Myocardial infarction or unstable cardiac angina within 6 months of screening.
Patients with underlying chronic liver disease (Child-Pugh A, B, or C hepatic impairment).
Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
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.
Life expectancy for a disease other than ILD < 2.5 years (Investigator assessment).
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.
Other investigational therapy was received within 1 month or 6 half-lives (whichever was greater) before the screening visit.
Previous treatment with nintedanib or pirfenidone (taken the drug for ≥ 1 month or history of intolerance/side effects)
Current or recent use of one or more of the following medications (See: SOC immunosuppression and washout under section 6.2 for details)
Cyclophosphamide within 3 months of baseline.
Rituximab within 4 weeks of baseline.
Anti-tumor necrosis factor (infliximab, golimumab, or certolizumab) within 8 weeks or adalimumab within 4 weeks, and etanercept within 2 weeks of baseline.
Janus kinase inhibitors (tofacitinib, upadacitinib, baricitinib, others) within 4 weeks of baseline.
Anakinra within 1 week of baseline.
Other biological agents such as tocilizumab, abatacept, etc. within 4 weeks of baseline.
Safety laboratory abnormality as any one of below
Aspartate transferase (AST), alanine aminotransferase (ALT) > 1.5 x ULN at screening, unless deemed due to active myositis, 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.
Bilirubin > 1.5 x ULN at screening
Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula at screening.
Hgb < 9.0
Platelet count < 100,000/mm3
White blood cells < 3000/mm3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	National Jewish Health	Denver	Colorado	United States	80206
3	University of Florida	Tampa	Florida	United States	33612
4	University of Chicago	Chicago	Illinois	United States	60637
5	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
6	Johns Hopkins University	Baltimore	Maryland	United States	21224
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Columbia University Irving Medical Center	New York	New York	United States	10032
9	Northwell Health	New York	New York	United States	11021
10	Cleveland Clinic	Cleveland	Ohio	United States	44195
11	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
12	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15216
13	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
14	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
15	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84112