Evaluation of Oral ORIN1001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Exclusion Criteria

• •1. Screening lab values that fail to meet the following criteria will render the subject ineligible for study participation:
• •* Platelet count \<100 × 109/L. Repeat measurements may be performed, but transfusion, in order to meet eligibility criteria, is not allowed.
• •* Hemoglobin \<12.9 g/dL (men) and \<11.9 g/dL (women).
• •* Prothrombin time (PT) or partial thromboplastin time (PTT) \>1.5 × upper limit of normal; international normalized ratio (INR) \>2.
• •* Aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \>1.5 × upper limit of normal (ULN).
• •* Serum glutamic-oxaloacetic transaminase \[SGOT\] or serum glutamic pyruvic transaminase \[SGPT\]) \>2.0 × ULN.
• •* Kidney disease with estimated glomerular filtration rate \<60 mL/min).
• •2. Forced vital capacity (FVC) ≤40% of predicted normal per site pulmonary function lab protocol.
• •3. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤30% of predicted normal as calculated according to the site pulmonary function lab protocol.
• •4. Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio \< 0.7.
• •5. Documented IPF exacerbation within 3 months of signing the ICF (e.g., \>5% or 10% change in FVC and DLCO, respectively).
• •6. Listing for lung transplantation, defined as the assignment of a lung allocation score or acceptance on the waiting list for lung transplantation.
• •7. Current and/or uncontrolled cardiovascular condition (e.g., clinically significant arrhythmia or hypertension), \>Class II heart failure per New York Heart Association criteria, unstable angina, myocardial infarction, coronary syndrome) within 6 months of Screening which, as judged by the Investigator, might put the subject at risk because of participation in the study.
• •8. Known cirrhotic liver, chronic liver, or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones). Liver cirrhosis with portal hypertension and active liver infection are exclusionary (note: cured hepatitis C is not considered active).
• •9. Gastrointestinal disease (e.g., active bleeding or ulcers) or procedure that could interfere with oral absorption or tolerance of the IMP, including difficulty swallowing.
• •10. Diarrhea \>Grade 1 (i.e., increase of \>4 stools per day OR \>1 watery stool per day OR moderate increase in ostomy output compared to baseline) will render a subject ineligible for participation in this study. Anti-diarrheal medication (e.g., loperamide, sold under the brand name Imodium®, among others) is allowed.
• •11. Active malignancy within the past 12 months or ongoing active cancer treatment (surgery, radiotherapy, chemotherapy or immunotherapy), except for adequately treated Stage 1 cancer, nonmelanoma skin cancer, or in situ cervical cancer. Cancer in complete remission or requiring only maintenance therapy (e.g., tamoxifen for breast cancer) is not considered active.
• •12. Known bleeding risk due to platelet dysfunction, or inherited or acquired clotting factor deficiency (e.g., von Willebrand disease, hemophilia).
• •13. Major trauma or surgery including but not limited to operations involving a major organ (e.g., the cranium, chest, abdomen, or pelvic cavity) OR requiring a lengthy recovery period (e.g., arthroplasty) within 3 months of signing the ICF; or expected surgery during the trial period.
• •14. Central nervous system hemorrhagic event within 12 months of signing ICF; brain arterio-venous malformation (AVM) or moderate-to-severe ischemic stroke within 6 months of signing ICF.
• •15. Concurrent use of full-dose therapeutic anti-coagulation (e.g., vitamin K antagonist, dabigatran, hirudin, direct factor Xa inhibitors) or high dose anti-platelet therapy. Aspirin \<81 mg/day, prophylactic subcutaneous (SC) heparin or SC low-molecular weight heparin for deep vein thrombosis prophylaxis or heparin flush to maintain intravenous catheter patency are allowed.
• •16. Long-term use of nonsteroidal anti-inflammatory agents, defined as \>4 days per week.
• •17. Receipt of hematopoietic growth factors, blood or blood product transfusion within 1 week of the first dose of IMP.
• •18. Disqualifying treatments within 60 days or 5 half-lives (whichever is longer) from Randomization include:
• •* Systemic corticosteroids (\>10 mg prednisone or equivalent).
• •* Systemic immunosuppressive therapy.
• •* Investigational agent other than study IMP.
• •19. Recreational drug use (including amphetamines, cocaine, barbiturates, opiates, benzodiazepines, phencyclidine, and cannabinoids) for the duration of study participation.
• •20. Clinically significant laboratory abnormality, medical or psychological comorbidity, or concurrent medication that could compromise subject safety, data integrity or requirements for study participation, per site Investigator in consultation with the Sponsor.
• •21. Inability to attend in-person appointments per current clinical site COVID-19 guidelines and restrictions.