Ifetroban for Pulmonary Fibrosis

Recruiting at 16 trial locations

Overseen By Ingrid Anderson, PhD, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ifetroban for individuals with idiopathic pulmonary fibrosis (IPF), a lung condition where scarring makes breathing difficult. Researchers aim to determine if taking ifetroban as a daily pill can safely and effectively slow down or prevent further lung damage. Participants will receive either ifetroban or a placebo (a harmless pill with no active drug) for 12 months. Individuals with a confirmed IPF diagnosis, who have had stable symptoms and treatment for at least two months, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ifetroban is under investigation for its potential to prevent and treat lung fibrosis, a condition where lung tissue becomes damaged and scarred. Ongoing studies aim to evaluate its safety and effectiveness, assessing how well it works and interacts with the body without causing harm.

Since this trial is in Phase 2, earlier tests produced positive results, warranting continuation. Although detailed safety data from previous studies isn't provided here, ifetroban's advancement in the trial stages suggests that its side effects might be manageable. As trials progress, more detailed information about side effects and overall tolerance will become available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Ifetroban is unique because it targets a different pathway than most current treatments for pulmonary fibrosis, which typically focus on reducing inflammation or suppressing the immune system. Ifetroban acts as a thromboxane receptor antagonist, which may help prevent fibrosis by blocking the pathways that lead to tissue scarring in the lungs. Researchers are excited about this treatment because it offers a novel approach that could complement or enhance existing therapies, potentially improving outcomes for patients with this challenging condition.

What evidence suggests that ifetroban might be an effective treatment for pulmonary fibrosis?

Research shows that ifetroban, which participants in this trial may receive, might help prevent and treat lung fibrosis, a condition where lung tissue becomes scarred and stiff. This drug has shown promise in addressing lung fibrosis caused by various factors, such as certain medications and radiation. The aim is to reduce lung scarring and ease breathing. While specific data on ifetroban's effectiveness for idiopathic pulmonary fibrosis (IPF) is still being collected, its ability to target fibrosis offers hope. Ongoing studies, including this trial, aim to confirm ifetroban's potential benefits for people with IPF. ^{1 2 4 6 7}

Who Is on the Research Team?

Todd Rice, MD, MSc

Principal Investigator

Cumberland Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ifetroban Sodium
• Placebo

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 safety analysis of 1299 patients with idiopathic pulmonary fibrosis (IPF) treated with pirfenidone, the drug was found to be safe and generally well tolerated over a median exposure of 1.7 years, with common mild to moderate side effects like nausea and rash.

Serious liver enzyme elevations occurred in only 3.1% of patients, and these were typically transient and reversible, indicating that while monitoring is necessary, significant long-term safety concerns are minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. Lancaster, L., Albera, C., Bradford, WZ., et al.[2022]

Pirfenidone effectively reduces bleomycin-induced pulmonary fibrosis in mice at a minimum dose of 30 mg/kg/day, demonstrating its potential as a treatment for fibrotic diseases like idiopathic pulmonary fibrosis.

Unlike prednisolone, which did not suppress pulmonary fibrosis, pirfenidone regulates key cytokines such as interferon-gamma, basic-fibroblast growth factor, and transforming growth factor-beta1, contributing to its antifibrotic effects.

NCBI (Pubmed)

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. Oku, H., Shimizu, T., Kawabata, T., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05571059

Study Details | NCT05571059 | Oral Ifetroban in Patients ... Ifetroban prevents and treats lung fibrosis due to multiple causes (bleomycin, genetic, radiation). The safety and efficacy of oral ifetroban will be assessed ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05571059

Oral Ifetroban in Patients With Idiopathic Pulmonary Fibrosis ... Ifetroban prevents and treats lung fibrosis due to multiple causes (bleomycin, genetic, radiation). The safety and efficacy of oral ifetroban will be assessed ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05571059?term=AREA%5BBasicSearch%5D(golden%20%20rice)&rank=5

Study Details | NCT05571059 | Oral Ifetroban in Patients ... Ifetroban prevents and treats lung fibrosis due to multiple causes (bleomycin, genetic, radiation). The safety and efficacy of oral ifetroban will be assessed ...

4. withpower.com withpower.com/trial/phase-2-lung-diseases-interstitial-2-2023-085fa

Ifetroban for Pulmonary Fibrosis Trial Overview The trial tests the safety and effectiveness of oral Ifetroban in treating IPF compared to a placebo. Participants will either receive Ifetroban ...

5. prnewswire.com prnewswire.com/news-releases/cumberland-pharmaceuticals-announces-fda-clearance-of-ind-for-new-treatment-of-idiopathic-pulmonary-fibrosis-301831813.html

CUMBERLAND PHARMACEUTICALS ANNOUNCES FDA ... The Company has designed a Phase II clinical trial to study the safety, tolerability, and efficacy of oral ifetroban in patients with IPF.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/443739

Oral Ifetroban in Patients With Idiopathic Pulmonary ... Ifetroban prevents and treats lung fibrosis due to multiple causes (bleomycin, genetic, radiation). The safety and efficacy of oral ifetroban will be assessed ...

7. investor.cumberlandpharma.com investor.cumberlandpharma.com/node/14596/pdf

Cumberland Pharmaceuticals Announces FDA Clearance Of ... The Company has designed a Phase II clinical trial to study the safety, tolerability, and efficacy of oral ifetroban in patients with IPF.