Pirfenidone for Pulmonary 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a drug called pirfenidone for individuals with advanced fibrotic sarcoidosis, a condition that causes lung scarring over time. Participants will receive either pirfenidone or a placebo (a pill with no active drug) to assess the impact on lung health. The trial targets those diagnosed with sarcoidosis, who have significant lung scarring, and are already on stable prednisone treatment. As a Phase 4 trial, pirfenidone has already received FDA approval and demonstrated effectiveness; this research aims to understand its benefits for a broader patient population.

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 is the safety track record for pirfenidone?

Research has shown that pirfenidone is generally safe for people. This medication is already approved for treating idiopathic pulmonary fibrosis, a lung disease. Studies have found that common side effects include nausea, diarrhea, tiredness, and dizziness. While these can be uncomfortable, they are usually manageable. No strong evidence links pirfenidone to serious side effects. This trial is in a later phase, indicating that the treatment has been tested on many people and is generally well-tolerated. Prospective participants should know that the treatment has a good safety record in previous studies. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for progressive fibrotic sarcoidosis, which often rely on corticosteroids and immunosuppressants to manage inflammation, pirfenidone offers a novel approach by directly targeting fibrotic pathways. Researchers are excited about pirfenidone because it has antifibrotic properties that may help slow or even reverse lung scarring, a critical concern in sarcoidosis. Additionally, pirfenidone is already used in treating idiopathic pulmonary fibrosis, suggesting it could bring a well-established safety profile to sarcoidosis treatment.

What is the effectiveness track record for pirfenidone in treating advanced fibrotic sarcoidosis?

Research has shown that pirfenidone, which participants in this trial may receive, can slow the decline in lung function and reduce the risk of sudden worsening in lung conditions. In studies, patients taking pirfenidone had better lung function and survival rates compared to those on a placebo. This drug has effectively treated conditions like idiopathic pulmonary fibrosis, which causes lung scarring. Although data for fibrotic sarcoidosis is limited, its success in treating similar lung issues suggests potential benefits. Overall, pirfenidone has shown promise in managing diseases with lung scarring. ^{6 7 8 9 10}

Who Is on the Research Team?

Robert P Baughman, MD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pirfenidone
• Placebos

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10642852/

Real world experience on the effectiveness and safety of ... Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients ...

2. esbriethcp.com esbriethcp.com/efficacy/clinical-trial-results.html

Clinical Trial Results for IPF | Esbriet® (pirfenidone) Esbriet® (pirfenidone) achieved a numerical difference in all-cause mortality in three phase 3 trials. No statistically significant difference over the study ...

3. publications.ersnet.org publications.ersnet.org/content/erj/47/1/243

analysis of pooled data from three multinational phase 3 trials Efficacy outcomes. Analysis of outcomes at 1 year demonstrated that pirfenidone reduced the proportion of patients with a ≥10% decline in FVC % pred or death by ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1402582

A Phase 3 Trial of Pirfenidone in Patients with Idiopathic ... Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00287729

NCT00287729 | Safety and Efficacy of Pirfenidone in ... The purposes of this study are to assess the efficacy of treatment with pirfenidone 2403 milligrams per day compared with placebo in patients with ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2014/022535orig1s000medr.pdf

022535Orig1s000 - accessdata.fda.gov Safety data showed that pirfenidone is most commonly associated with nausea, diarrhea, dyspepsia, vomiting, fatigue, anorexia, dizziness ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/pirfenidone-oral-route/description/drg-20122610

Pirfenidone (oral route) - Side effects & dosage Pirfenidone is used to treat idiopathic pulmonary fibrosis. This medicine is available only with your doctor's prescription.

8. en.wikipedia.org en.wikipedia.org/wiki/Pirfenidone

Pirfenidone Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7561536/

Benefits of prolonged-release pirfenidone plus standard of ... Conclusions. PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. Trial registration. Clinical trial number ...

10. webmd.com webmd.com/drugs/2/drug-165321/pirfenidone-oral/details

Pirfenidone (Esbriet) - Uses, Side Effects, and More Find patient medical information for Pirfenidone (Esbriet) on WebMD including its uses, side effects and safety, interactions, pictures,