Pirfenidone for Progressive Fibrotic Sarcoidosis

(PirFS Trial)

Overseen By Rebecca Reeves

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Cincinnati

Must be taking: Prednisone

Must not be taking: Pulmonary hypertension therapy

Disqualifiers: Liver disease, Heart failure, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of prednisone for at least two months before joining, and you should not change other immunosuppressive medications during that time. The protocol does not specify about other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Pirfenidone?

Research shows that Pirfenidone helps slow down the progression of idiopathic pulmonary fibrosis (IPF), a lung disease, by reducing lung function decline and improving survival rates. It also helps patients maintain their ability to walk longer distances and manage symptoms better over a year. ^{1 2 3 4 5}

Is pirfenidone generally safe for humans?

Pirfenidone has been studied for safety in people with idiopathic pulmonary fibrosis (a lung disease) and is generally considered safe, but it can cause side effects. Common side effects include nausea, rash, and fatigue, and managing these can help improve treatment adherence. ^{3 6 7 8 9}

What makes the drug Pirfenidone unique compared to other treatments?

Pirfenidone is unique because it works by reducing fibrosis (scarring) and inflammation in the lungs, which is different from many other treatments that primarily focus on managing symptoms. It is taken orally, which can be more convenient compared to treatments that require injections or infusions. ^{10 11 12 13 14}

What is the purpose of this trial?

This trial is testing pirfenidone, a medication that may help people with severe lung scarring due to advanced fibrotic sarcoidosis. The drug aims to reduce inflammation and prevent further lung damage, making it easier for patients to breathe. Pirfenidone has been shown to slow the progression of idiopathic pulmonary fibrosis and has potential benefits in other fibrosing interstitial lung diseases.

Research Team

Robert P Baughman, MD

Principal Investigator

University of Cincinnati

Eligibility Criteria

Inclusion Criteria

Diagnosis of sarcoidosis

Pulmonary function testing with a Composite Physiologic Index (CPI) score of greater than 40

Patient must have evidence of >20% fibrosis on high resolution cat scan

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either pirfenidone or placebo, with dosage titration over several weeks

2 years

Regular visits for titration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pirfenidone
• Placebos

Participant Groups

Group I: Pirfenidone Active Control 1 Intervention

Pirfenidone titrated to three 267 mg tablets three times a day

Group II: Placebos Placebo Group 1 Intervention

Placebo titrated to three tablets three times a day

Pirfenidone is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in United States as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in Canada as Esbriet for:

• Idiopathic Pulmonary Fibrosis

Approved in Japan as Pirespa for:

• Idiopathic Pulmonary Fibrosis

Approved in China as Etuary for:

• Idiopathic Pulmonary Fibrosis

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Royal Brompton & Harefield NHS Foundation Trust

Collaborator

Trials

236

Recruited

150,000+

Findings from Research

In a pooled analysis of data from three phase 3 trials involving 1247 patients with idiopathic pulmonary fibrosis (IPF), pirfenidone significantly reduced the risk of disease progression, showing a 43.8% decrease in patients experiencing a ≥10% decline in lung function or death after one year.

While pirfenidone was effective in slowing disease progression and improving outcomes like walking distance and breathlessness, it was associated with more gastrointestinal and skin-related side effects, although these rarely led to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Noble, PW., Albera, C., Bradford, WZ., et al.[2022]

In a study of 31 patients with acute exacerbation of interstitial pneumonia (AE-IP), the administration of pirfenidone (PFD) did not significantly improve survival rates compared to those not receiving PFD, with survival rates of 78.6% vs 64.7% at 30 days and 64.3% vs 52.9% at 90 days.

However, patients receiving PFD showed a significant reduction in inflammation, as indicated by lower white blood cell counts and C-reactive protein levels, suggesting that PFD may help manage inflammation in AE-IP patients undergoing corticosteroid treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of pirfenidone in patients with an acute exacerbation of interstitial pneumonia. Matsumura, T., Tsushima, K., Abe, M., et al.[2018]

A survey of 169 pulmonologists revealed that gastrointestinal intolerance is a key concern when starting pirfenidone for idiopathic pulmonary fibrosis, leading to the use of alternative titration schedules to help patients reach the full dose.

Strategies to manage side effects included advising patients to take pirfenidone with substantial meals to reduce gastrointestinal issues and recommending sun protection measures to address photosensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Wencel, ML., Haselkorn, T., Limb, SL., et al.[2021]

In a meta-analysis of six randomized controlled trials involving 1073 participants, pirfenidone (PFD) was found to have a significantly higher rate of adverse events compared to placebo, leading to more patients discontinuing the treatment.

Common adverse effects associated with PFD included gastrointestinal issues (like nausea and diarrhea), neurological symptoms (such as dizziness and fatigue), and dermatological reactions (including photosensitivity), indicating that while PFD is used for pulmonary fibrosis, it may not be well-tolerated by all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials. Jiang, C., Huang, H., Liu, J., et al.[2022]

Pirfenidone is an effective treatment for idiopathic pulmonary fibrosis (IPF), shown to reduce lung function decline, decrease mortality, and improve progression-free survival based on randomized controlled trials and real-world studies.

To maximize the benefits of pirfenidone, it is crucial to manage its potential adverse events, and the review outlines strategies for preventing and managing these side effects to enhance patient adherence to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Lancaster, LH., de Andrade, JA., Zibrak, JD., et al.[2022]

A comprehensive safety analysis of pirfenidone, involving 789 patients over a median exposure of 2.6 years, shows that it is generally safe and well tolerated for treating idiopathic pulmonary fibrosis (IPF).

The most common side effects were mild to moderate gastrointestinal and skin-related events, with serious liver enzyme elevations occurring in only 2.7% of patients, indicating a low risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Valeyre, D., Albera, C., Bradford, WZ., et al.[2022]

In a study of 56 myelofibrosis patients treated with ruxolitinib, the presence of multiple gene mutations, particularly high-risk mutations, was associated with shorter treatment duration and progression-free survival, indicating a reduced efficacy of the drug.

Ruxolitinib was less effective in reducing spleen size and improving symptoms in patients with specific mutations (ASXL1, EZH2, SRSF2), highlighting the importance of genetic profiling in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology]. Tan, YX., Luo, J., Huang, JX., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone. [2020]

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

Expert consensus on the management of adverse events and prescribing practices associated with the treatment of patients taking pirfenidone for idiopathic pulmonary fibrosis: a Delphi consensus study. [2022]

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

The effects of pirfenidone in patients with an acute exacerbation of interstitial pneumonia. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pirfenidone: a review of its use in idiopathic pulmonary fibrosis. [2018]

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

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. [2021]

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

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials. [2022]

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

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. [2022]

9. Australia pubmed.ncbi.nlm.nih.gov

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. [2022]

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

Peginesatide: a potential erythropoiesis stimulating agent for the treatment of anemia of chronic renal failure. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Ruxolitinib in myelofibrosis: to be or not to be an immune disruptor. [2020]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of eculizumab in paroxysmal nocturnal hemoglobinuria patients with or without aplastic anemia: prospective study of a Korean PNH cohort. [2020]

14. China pubmed.ncbi.nlm.nih.gov

[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology]. [2023]