Oral Ifetroban in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Purpose
Ifetroban prevents and treats lung fibrosis due to multiple causes (bleomycin, genetic, radiation). The safety and efficacy of oral ifetroban will be assessed in patients with IPF.
Condition
- Idiopathic Pulmonary Fibrosis
Eligibility
- Eligible Ages
- Between 40 Years and 80 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female age 40 years or older 2. IPF Diagnosis: 1. Satisfying the 2022 American Thoracic Society/European Respiratory Society /Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) diagnostic criteria (Raghu 2022) confirmed by the investigator 2. UIP or probable UIP based on chest HRCT obtained within 2 months of Day 0, or historical lung biopsy consistent with UIP. 3. If receiving antifibrotic agents pirfenidone or nintedanib, patients must be receiving a stable dose for ≥ 2 months prior to Day 0 and planning to stay on stable background therapy; if not receiving pirfenidone or nintedanib, patients must be naive to both drugs or not have received either for at least 4 weeks prior to Day 0 and remain off background therapy with no intention to start or re-start (combination of nintedanib and pirfenidone not allowed). 4. If receiving monotherapy for the treatment of pulmonary hypertension (e.g. phosphodiesterase 5 inhibitors, endothelin receptor antagonists or inhaled or oral prostanoid therapy), patients must be receiving a stable dose for ≥ 4 weeks prior to Day 0 and planning to remain on a stable dose throughout the study. 5. FVC ≥ 40% of predicted normal according to Global Lung Initiative (GLI) 6. Diffusion Capacity of Carbon Monoxide (DLCO) [corrected for hemoglobin] ≥ 25% to <80% of predicted normal
Exclusion Criteria
- Relevant airways obstruction (pre-bronchodilator Forced Expiratory Volume in one second to forced vital capacity ratio less than 70% (FEV1/FVC < 0.7)) 2. In the opinion of the Investigator, other clinically significant pulmonary abnormalities. 3. Known significant PAH, defined as previous clinical or echocardiographic evidence of significant right heart failure, history of right heart catheterization showing a cardiac index < 2 L/min/m2, or PAH requiring combination of PAH-specific therapies or any PAH parenteral therapy. 4. Emphysema ≥ 50% on HRCT assessed by the investigator, or the extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent chest HRCT. 5. Acute IPF exacerbation within 6 weeks prior to screening and/or during the screening period (investigator-determined). 6. ILD associated with other known causes 7. Lower respiratory tract infection requiring antibiotics within 4 weeks prior to Day 0 and/or during the screening period. 8. Major surgery (major according to the investigator's assessment) performed within six weeks prior to Day 0 or planned during the course of the trial. (Being on a transplant list is allowed). 9. AST or ALT > 1.5 x ULN, Bilirubin > 1.5 x ULN, Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula. 10. Underlying chronic liver disease (Child Pugh A, B or C hepatic impairment). 11. Cardiovascular diseases, any of the following: 1. Severe hypertension, uncontrolled despite treatment (≥160/100 mmHg) 2. Myocardial infarction within 6 months of Day 0 3. Unstable cardiac angina 12. Bleeding risk, any of the following: a. Known genetic predisposition to bleeding. b. Patients who require: i. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, direct oral anticoagulants, heparin, hirudin) ii. High dose antiplatelet therapy (> 325 mg/day of aspirin; > 75 mg/day ticlodipine or clopidogrel; any dose of other 2b3a anti-platelet agents) 13. History of hemorrhagic central nervous system (CNS) event within 12 months of Day 0 14. Any of the following within 3 months of Day 0: 1. Hemoptysis or hematuria 2. Active gastro-intestinal (GI) bleeding needing hospitalization/intervention or peptic ulcer disease 15. Coagulation parameters: International normalized ratio (INR) >2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN [Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. less than or equal to enoxaparin 40 mg s.c. per day or heparin 5000 units s.c. every 8 hours), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid (ASA) up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited]. 16. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Day 0 17. Use of disease-modifying antirheumatic drugs, B-cell depleting therapies or immunosuppressive medications, within 6 months of Day 0. 18. Use of systemic corticosteroids equivalent to prednisone >15mg/day within 2 weeks of Day 0. 19. Simultaneous use of pirfenidone and nintedanib at screening. 20. Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial. 21. Any documented active or suspected malignancy within 5 years prior to Day 0, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or "under surveillance" prostate cancer. 22. Evidence of active infection (chronic or acute) based on clinical exam or laboratory findings. 23. Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior). 24. The patient has a confirmed infection with Severe Acute Respiratory Syndrome- Coronvirus-2 (SARS-CoV-2) within the 4 weeks prior to Day 0 or during the screening period. 25. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. 26. Women of childbearing potential* not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently for 28 days prior to and 3 months after IMP administration. 27. In the opinion of the Investigator, active alcohol or drug abuse. 28. Patients not able to understand or follow trial procedures including completion of self- administered questionnaires without help. - 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Randomized, Double-Blind, Placebo-Controlled
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Each individual bottle is labelled with a unique numeric code that identifies the contents to the unblinded sponsor representative.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Ifetroban Sodium |
Drug: Ifetroban Oral capsule, 250 mg, once daily for 12 months |
|
|
Placebo Comparator Placebo |
Drug: Placebo Matching placebo, oral capsule, once daily for 12 months |
|
Recruiting Locations
Indiana University Health
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
University of Louisville
Louisville, Kentucky 40202
Louisville, Kentucky 40202
Beaumont Hospital, Royal Oak
Royal Oak, Michigan 48073
Royal Oak, Michigan 48073
Icahn School of Medicine at Mount Sinai
New York, New York 10029
New York, New York 10029
University of Rochester
Rochester, New York 14642
Rochester, New York 14642
More Details
- NCT ID
- NCT05571059
- Status
- Recruiting
- Sponsor
- Cumberland Pharmaceuticals
Detailed Description
This is a multicenter, prospective, randomized, placebo-controlled, phase II study to determine the safety and efficacy of oral ifetroban compared to placebo in subjects with IPF. Patients who meet the inclusion criteria and none of the exclusion criteria will receive oral ifetroban or placebo once daily for 12 months. Subjects will be randomly assigned to one of two oral treatment groups: ifetroban or placebo and block randomized by background therapy. All subjects who receive treatment will be assessed for safety. All subjects with at least one efficacy assessment post-baseline will be evaluated for efficacy. Blood and urine will be collected for standard and novel PPF biomarkers.