Ifetroban for Pulmonary Fibrosis

Recruiting at 15 trial locations

Overseen by Todd Rice, MD, MSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Cumberland Pharmaceuticals

Must be taking: Antifibrotics, Pulmonary hypertension monotherapy

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Pulmonary abnormalities, Cardiovascular diseases, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial does not require you to stop your current medications if you are on a stable dose of antifibrotic agents like pirfenidone or nintedanib, or monotherapy for pulmonary hypertension. However, if you are not on these medications, you must not have taken them for at least 4 weeks before starting the trial.

What data supports the effectiveness of the drug Ifetroban for treating pulmonary fibrosis?

Research shows that Ifetroban, a TBXA2R antagonist, reduced harmful signaling in the lungs and protected mice from lung fibrosis in several preclinical models, suggesting it might help treat pulmonary fibrosis. ^{1 2 3 4 5}

How does the drug Ifetroban Sodium differ from other treatments for pulmonary fibrosis?

Ifetroban Sodium is unique because it is being studied specifically for pulmonary fibrosis, whereas other treatments like pirfenidone are primarily used for idiopathic pulmonary fibrosis and work by slowing disease progression. Ifetroban's distinct mechanism of action or benefits in this condition are not detailed in the available research, making it a novel option under investigation. ^{1 6 7 8 9}

Research Team

Todd Rice, MD, MSc

Principal Investigator

Cumberland Pharmaceuticals

Eligibility Criteria

This trial is for men and women over 40 with Idiopathic Pulmonary Fibrosis (IPF) who meet specific diagnostic criteria. They should have a certain lung function level, may be on stable doses of antifibrotic agents or treatment for pulmonary hypertension, but not have significant emphysema or recent major health events like surgery or heart disease.

Inclusion Criteria

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 UIP or probable UIP based on chest HRCT obtained within 2 months of Day 0, or historical lung biopsy consistent with UIP.

I have been on a stable dose of pirfenidone or nintedanib for 2 months, or I haven't taken them at all.

FVC ≥ 40% of predicted normal according to Global Lung Initiative (GLI)

Exclusion Criteria

I have not had cancer or an active infection in the last 5 years.

Pregnancy, nursing, or unwillingness to use effective birth control methods

I recently had a sudden worsening of my lung condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral ifetroban or placebo once daily for 12 months

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ifetroban Sodium (Prostaglandin Receptor Antagonist)
• Placebo (Drug)

Trial Overview The trial tests the safety and effectiveness of oral Ifetroban in treating IPF compared to a placebo. Participants will either receive Ifetroban Sodium or an inactive substance without knowing which one they are taking to measure true effects.

Participant Groups

Group I: Ifetroban Sodium Experimental Treatment 1 Intervention

Drug: Ifetroban Oral capsule, 250 mg, once daily for 12 months

Group II: Placebo Placebo Group 1 Intervention

Drug: Placebo Matching placebo, oral capsule, once daily for 12 months

Who Is Running the Clinical Trial?

Cumberland Pharmaceuticals

Lead Sponsor

Trials

63

Recruited

9,400+

A.J. Kazimi

Cumberland Pharmaceuticals

Chief Executive Officer since 1999

B.S. from the University of Notre Dame, MBA from Vanderbilt University Owen Graduate School of Management

Ines Macias-Perez

Cumberland Pharmaceuticals

Chief Medical Officer

Ph.D. in Cancer Biology from Vanderbilt University

Findings from Research

In a study of 92 patients with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone, the drug showed an acceptable safety profile, with skin-related (25%) and gastrointestinal (17.5%) adverse events being the most common, leading to discontinuation in 22.5% of cases.

Despite some patients experiencing significant improvements in lung function, the overall decline in lung function (%FVC and %DLCO) was noted over 36 months, highlighting the need for further research through prospective observational registries to better understand pirfenidone's long-term efficacy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. Tzouvelekis, A., Karampitsakos, T., Ntolios, P., et al.[2022]

TBXA2R is upregulated in lung fibroblasts during idiopathic pulmonary fibrosis (IPF) and plays a critical role in fibroblast activation, as shown in studies involving both human and mouse lung tissues.

Using a TBXA2R antagonist, ifetroban, demonstrated protective effects against lung fibrosis in multiple preclinical models, suggesting that targeting TBXA2R could be a promising therapeutic strategy for treating pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis. Suzuki, T., Kropski, JA., Chen, J., et al.[2023]

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a median survival of only about 3 years after diagnosis, highlighting the urgent need for effective treatments.

Bosentan, an endothelin receptor antagonist, did not show overall benefit in a recent trial for IPF, but a post hoc analysis suggests it may be effective in a specific subgroup of patients with biopsy-proven IPF and minimal honeycombing, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of bosentan for idiopathic pulmonary fibrosis. Swigris, JJ., Brown, KK.[2010]

In a mouse model of bleomycin-induced pulmonary fibrosis, the AT1 antagonist olmesartan significantly reduced lung fibrosis scores and levels of inflammatory cytokines, indicating its efficacy in mitigating lung damage.

The AT2 antagonist PD-123319 also reduced lung fibrosis and inflammatory cell counts, suggesting that both AT1 and AT2 receptors play roles in the progression of pulmonary fibrosis through different mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice. Waseda, Y., Yasui, M., Nishizawa, Y., et al.[2021]

External controls (ECs) derived from historical randomized clinical trials (RCTs) showed comparable treatment effects to the original BMS-986020 trial for idiopathic pulmonary fibrosis (IPF), indicating their potential utility in enhancing trial efficiency.

In contrast, ECs from real-world data sources, such as registries and electronic health records, demonstrated a slower rate of lung function decline compared to the placebo group, suggesting they may not provide reliable comparability for evaluating new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. Swaminathan, AC., Snyder, LD., Hong, H., et al.[2023]

Three patients with pulmonary fibrosis following H1N1 ARDS showed positive responses to a treatment regimen including pirfenidone, azithromycin, and prednisolone, leading to symptomatic improvement and better lung function over one year.

The combination therapy resulted in regression of lung opacities and no progression of fibrosis on CT scans, suggesting that this treatment approach warrants further investigation for managing pulmonary fibrosis in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined pirfenidone, azithromycin and prednisolone in post-H1N1 ARDS pulmonary fibrosis. Saha, A., Vaidya, PJ., Chavhan, VB., et al.[2020]

In a study of 20 patients with idiopathic pulmonary fibrosis (IPF), treatment with Interferon gamma-1b for 12 months significantly reduced levels of angiogenic chemokines (IL-8, ENA-78, and GRO-alpha), suggesting a potential mechanism for its effects on vascular remodeling in the disease.

Despite the decrease in angiogenic factors, the treatment did not significantly alter levels of angiostatic chemokines, except for a notable reduction in MIG, which may help explain the limited therapeutic benefits of Interferon gamma-1b in managing IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients. Antoniou, KM., Tzanakis, N., Tzortzaki, EG., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of bosentan for idiopathic pulmonary fibrosis. [2010]

4. England pubmed.ncbi.nlm.nih.gov

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Combined pirfenidone, azithromycin and prednisolone in post-H1N1 ARDS pulmonary fibrosis. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients. [2022]