The Study Will Evaluate the Use of Nintedanib in Slowing Lung Fibrosis in Patients With Pulmonary Infiltrates Related to COVID-19
The Study Will Evaluate the Use of Nintedanib in Slowing Lung Fibrosis in Patients With Pulmonary Infiltrates Related to COVID-19
This is a collaborative study between Icahn School of Medicine at Mount Sinai and Boehringer
 Ingelheim Pharmaceuticals to determine the effect of Nintedanib on slowing the rate of lung
 fibrosis in patients who have been diagnosed with COVID-19, and have ongoing lung injury more
 than 4 weeks out from their diagnosis.
The purpose of this study is to determine the efficacy of the study drug, Nintedanib, on
 slowing the rate of lung fibrosis in patients who are noted to have infiltrates, or ongoing
 lung injury, on chest x-ray/CT 4 weeks or longer from their initial symptoms. In addition,
 the study will also investigate patient reported outcomes using questionnaires, and the
 safety and tolerability of the study drug. Blood specimens will be collected to assess
 biomarkers and monitor drug safety.

 The trial will be randomized 1:1 between Nintedanib and placebo.

 Nintedanib has been approved by the FDA for the treatment of chronic fibrosing ILD with a
 progressive phenotype, but has not been studies in patients with post COVID 19 lung fibrosis.

 Subjects participating in this study will:

 -  Attend in person visits to the study doctor's office on the date of enrollment, 15 days
 after enrollment, 45 days after enrollment, 90 days after enrollment, 135 days after
 enrollment, and 180 days after enrollment. If the participant is being enrolled in the
 study while hospitalized at Mount Sinai, the study doctor will travel to the hospital
 room.

 -  Undergo a HRCT (High-resolution computed tomography) scan of the chest within 14 days of
 enrollment, and then again at 180 days after enrollment.

 -  Have Pulmonary Function Tests within 14 days of enrollment, and then again 45, 90, 135
 and 180 days after enrollment.

 -  Have blood drawn routinely while participating in this study (15 days after starting
 medication, then again on day 45, 90, 135 and 180).

 -  Participants will not pay for physician visits, blood draws, breathing tests, CT scans
 or the medication for this study. Participants will receive a stipend to cover the
 transportation costs for your visits.

 The main risks to participants are:

 1. Common side effects include: nausea, vomiting, diarrhea, stomach discomfort

 2. Loss of appetite and weight loss

 3. Liver function abnormalities (blood work will be monitored periodic intervals at
 scheduled blood draws as listed above)

 4. Slightly higher risk of bleeding

 5. Slightly higher risk of blood clots that can form in the blood vessels that supply
 oxygen to vital organs such as the brain and heart

 Benefits from participation in this research include the possibility that Nintedanib may slow
 down/prevent progression of lung fibrosis. If the lungs can heal without fibrosis, this may
 result in fewer symptoms of shortness of breath, cough and need for added oxygen.

 Instead of participating in this research, subjects may choose to monitor their lung
 condition with their doctor or participate in another research study.
Inclusion Criteria:

 -  Willing and able to provide written informed consent

 -  Subjects Age > 18

 -  Initial SARS-CoV-2 infection confirmed by PCR test or positive serologies

 -  Have findings consistent with fibrosis found on CT scan (these may include
 reticulations, traction bronchiectasis, septal thickening, and early honeycombing)

 -  Required one of the following after diagnosis with SARS-CoV-2: supplemental oxygen by
 nasal cannula, high flow oxygen, non invasive ventilation such as CPAP or BIPAP, or
 mechanical ventilation

 -  Are 30 days from onset of initial SARS-CoV-2 symptoms

 -  Forced Vital Capacity less than 80% predicted based on ATS/ERS criteria or DLCO<60%

 -  Women of childbearing potential who agree to use of highly effective contraception
 during treatment and for three months following the last dose of nintedanib

 Exclusion Criteria:

 Candidates will be excluded from study entry if any of the following exclusion criteria
 exist at the time of the Screening Visit (prior to randomization):

 -  Co-administration of other investigational agents against COVID-19

 -  Active SARS-CoV-2 infection based on clinical judgment

 -  Currently Pregnant or Breast Feeding

 -  Current Use of Prednisone or equivalent > 10 mg/daily

 -  Use of full dose anticoagulation therapy or high dose anti platelet drug therapy at
 screening (at the discretion of the investigator, anticoagulation therapy may be added
 if clinically indicated)

 -  History of myocardial infarction within past 90 days

 -  Life threatening bleed

 -  Hemodynamic instability or shock

 -  Superimposed pulmonary bacterial infection

 -  Pre-existing interstitial lung disease

 -  Active Hep A/B/C hepatitis as measured with PCR for viral load and/or serologies

 -  Pre-existing liver disease: Including Abnormal Laboratory Liver Function: Childs Pugh
 B/C, AST/ALT > 3 times the upper limit of normal (ULN). If Child Pugh A, can
 participate on Nintedanib 100 mg by mouth twice daily.

 -  Subjects with a Creatinine clearance <30 ml/min or currently on hemodialysis

 -  Inability to tolerate orally administered medication (medication must be taken with
 meals)