AP01 for Pulmonary Fibrosis

Recruiting in Palo Alto (17 mi)

+103 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Avalyn Pharma Inc.

Must be taking: Nintedanib

Must not be taking: Oral pirfenidone

Disqualifiers: Idiopathic pulmonary fibrosis, Renal disease, others

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of 2 doses of inhaled pirfenidone (AP01) versus placebo on top of standard of care in participants with PPF over 52 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants already on nintedanib must have been on it for at least 6 months, or off it for at least 12 weeks if discontinued. You cannot be on oral pirfenidone or have taken it within 3 months before the trial.

What data supports the effectiveness of the drug AP01, Inhaled Pirfenidone, for treating pulmonary fibrosis?

Pirfenidone, a component of AP01, has been shown to slow the progression of idiopathic pulmonary fibrosis, a type of lung disease, and is approved for this use by health authorities. It has also shown potential benefits in other fibrotic conditions, suggesting it may help in treating pulmonary fibrosis. ^{1 2 3 4 5}

What is known about the safety of AP01 (Inhaled Pirfenidone) for pulmonary fibrosis?

Pirfenidone, used for pulmonary fibrosis, has a well-known safety profile from clinical trials and real-world studies. Common side effects include stomach upset, rash, and sensitivity to sunlight, which can be managed by taking the medication with food and using sun protection. ^{6 7 8 9 10}

How is the drug AP01 (Inhaled Pirfenidone) different from other treatments for pulmonary fibrosis?

AP01 is unique because it is an inhaled form of pirfenidone, which is traditionally taken orally. This inhalation method may offer a more direct delivery to the lungs, potentially reducing systemic side effects compared to the oral version. ^{2 4 7 11 12}

Research Team

Avalyn Pharma, Inc.

Principal Investigator

Avalyn Pharma Inc.

Eligibility Criteria

This trial is for people with Progressive Pulmonary Fibrosis who have worsening respiratory symptoms, an FVC of at least 45%, and a DLCO of at least 30%. Those on nintedanib must meet specific criteria related to their treatment duration and stability. Participants need to be able to perform acceptable spirometry tests.

Inclusion Criteria

I have been taking nintedanib for 6-12 months without changing the dose for the last 3 months.

Participant meets criteria for PPF as follows:

I stopped taking nintedanib at least 12 weeks ago.

Exclusion Criteria

Greater extent of emphysema than of fibrotic ILD on HRCT

I have been taking pirfenidone in the last 3 months.

Participants who cannot meet protocol-specified Baseline stability criteria

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AP01 high dose, AP01 low dose, or placebo for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AP01 (Anti-fibrotic agent)

Trial Overview The study is testing the safety and effectiveness of two doses of AP01 compared to a placebo in addition to standard care over one year. It's randomized, meaning participants are put into groups by chance, double-blind so neither they nor the researchers know who gets what, and placebo-controlled for comparison.

Participant Groups

Group I: AP01 Low Dose BID Experimental Treatment 1 Intervention

Pirfenidone Solution for Inhalation

Group II: AP01 High Dose BID Experimental Treatment 1 Intervention

Pirfenidone Solution for Inhalation

Group III: Placebo BID Placebo Group 1 Intervention

Placebo solution for inhalation

Who Is Running the Clinical Trial?

Avalyn Pharma Inc.

Lead Sponsor

Trials

1

Recruited

300+

DevPro Biopharma

Industry Sponsor

Trials

5

Recruited

800+

DevPro Biopharma

Collaborator

Trials

5

Recruited

800+

Findings from Research

Pirfenidone, already approved for idiopathic pulmonary fibrosis (IPF), is being studied for its potential effectiveness in treating other progressive fibrotic lung diseases that do not respond well to conventional anti-inflammatory therapies.

The study will focus on patients with various types of lung fibrosis, ensuring they have shown significant disease progression despite standard treatments, which highlights the urgent need for new therapies in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial. Behr, J., Neuser, P., Prasse, A., 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]

In a study of 281 patients with advanced liver fibrosis, those treated with prolonged-release pirfenidone (PR-PFD) showed a significant reduction in fibrosis (35%) compared to only 4.1% in patients receiving standard care, indicating its efficacy in treating this condition.

PR-PFD treatment also led to improvements in quality of life scores and was generally safe, with only 12% of patients reporting mild side effects like transient burning or nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study. Poo, JL., Torre, A., Aguilar-Ramírez, JR., et al.[2021]

In a study involving 13 patients with idiopathic pulmonary fibrosis (IPF), pirfenidone treatment did not significantly reduce the number of fibroblast foci, indicating that its anti-fibrotic effects may not be immediately observable in tissue samples after 6 months.

Despite the lack of significant changes in fibroblast foci and proliferation markers, the treatment was well-tolerated, and there was an increase in certain cytokines associated with angiogenesis and anti-inflammation, suggesting potential immunomodulatory effects of pirfenidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. Ronan, N., Bennett, DM., Khan, KA., et al.[2019]

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]

Pirfenidone is an effective treatment for idiopathic pulmonary fibrosis (IPF), as it significantly reduces lung function decline, improves progression-free survival, and lowers the risk of all-cause mortality after one year, based on randomized controlled trials.

The treatment has a favorable safety profile, but common side effects like gastrointestinal upset, rash, and photosensitivity require management strategies, such as taking the medication with food and using sun protection, to help patients continue their therapy long-term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. Cottin, V., Maher, T.[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 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]

References

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

Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study. [2022]

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

Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study. [2021]

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

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. [2019]

6. 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]

7. 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]

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

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

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. [2022]

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

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

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