AP01 for Pulmonary Fibrosis

Recruiting at 155 trial locations

Overseen By Daniele Tompkins

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Avalyn Pharma Inc.

Must be taking: Nintedanib

Must not be taking: Oral pirfenidone

Disqualifiers: Idiopathic pulmonary fibrosis, Renal disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

375 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaled treatment called AP01 (Inhaled Pirfenidone) for pulmonary fibrosis, a condition where lung tissue becomes damaged and scarred, making breathing difficult. Researchers aim to determine if AP01 can effectively and safely help people with this condition. Participants will receive either a low or high dose of AP01 or a placebo (a non-active treatment) alongside their regular care. The trial seeks individuals who have experienced worsening symptoms of pulmonary fibrosis despite previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that AP01 is likely to be safe for humans?

Research has shown that inhaled pirfenidone (AP01) is generally safe for long-term use. Studies have monitored its use for up to 240 weeks and found it well-tolerated. In related studies involving patients with idiopathic pulmonary fibrosis, AP01 was tested in two different doses. After 24 weeks, it proved safe and tolerable for most participants.

Some side effects have been reported with the oral form of pirfenidone, which is similar to AP01. However, the inhaled version, AP01, is designed to reduce these side effects. While some individuals might experience mild issues, serious side effects seen with the oral version are less likely with inhaled AP01. Overall, evidence suggests that AP01 is safe for humans, but monitoring for any side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary fibrosis, which often involve oral medications like pirfenidone and nintedanib, the study drug AP01 is delivered directly to the lungs as an inhalable solution. This unique delivery method could potentially reduce side effects associated with systemic administration and enhance drug concentration right where it's needed most. Researchers are excited about AP01 because it uses pirfenidone in a more targeted way, possibly improving lung function and slowing disease progression more effectively than existing options.

What evidence suggests that AP01 might be an effective treatment for pulmonary fibrosis?

Research shows that inhaled pirfenidone (AP01), which participants in this trial may receive, may help slow the worsening of lung function in people with idiopathic pulmonary fibrosis (IPF). Earlier studies found that oral pirfenidone can slow lung damage and reduce death rates in IPF patients. The inhaled form, such as AP01, aims to offer similar benefits while reducing side effects associated with systemic distribution. Long-term evidence suggests that AP01 remains effective over time and is generally safe. These findings offer hope for those with pulmonary fibrosis by potentially improving lung health and overall outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Avalyn Pharma, Inc.

Principal Investigator

Avalyn Pharma Inc.

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AP01

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 study of 338 patients with idiopathic pulmonary fibrosis (IPF), pirfenidone significantly reduced the annual decline in lung function (measured by forced vital capacity) regardless of whether patients were on a standard or lower dose, indicating its efficacy in slowing disease progression.

The safety profile of pirfenidone was consistent across different doses, with adverse events being more common in patients with more severe disease (GAP stages II-III), suggesting that while the drug is effective, monitoring for side effects is important, especially in advanced stages of IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study. Hwang, H., Lee, JK., Choi, SM., et al.[2022]

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]

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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06329401

A Study Evaluating the Safety and Efficacy of Inhaled AP01 ...

This is a randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of 2 doses of AP01 (pirfenidone solution for ...

2.

atsjournals.org

atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A2906

American Journal of Respiratory and Critical Care Medicine

Over up to 240 weeks follow up, AP01 appears to have continuing efficacy with a stable safety profile over the long-term of open-label treatment.

3.

thorax.bmj.com

thorax.bmj.com/content/78/9/882

Inhaled pirfenidone solution (AP01) for IPF: a randomised ...

Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side ...

4.

avalynpharma.com

avalynpharma.com/wp-content/uploads/2024/05/ERS-2023-poster-PA3485-FVC-in-ATLAS-vs-published-placebo.pdf

Inhaled pirfenidone (AP01) forced vital capacity (FVC) data ...

Placebo groups were collected from available data for 4 reference studies —. INPULSIS-1 and INPULSIS-2 (2), INBUILD (3) and ASCEND (4).

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36948586/

Inhaled pirfenidone solution (AP01) for IPF: a randomised ...

Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side ...

6.

avalynpharma.com

avalynpharma.com/wp-content/uploads/2023/02/ATS2023-poster-long-term-data-from-IPF-and-PPF-participants-in-AP01-005.pdf

Long-term Safety Data of Inhaled Pirfenidone (AP01) in ...

Oral pirfenidone reduces FVC decline compared to placebo in Idiopathic. Pulmonary Fibrosis (IPF), albeit with side effects1. AP01 is an aqueous pirfenidone ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06329401

A Study Evaluating the Safety and Efficacy of Inhaled AP01 ...

This is a randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of 2 doses of AP01 (pirfenidone solution for ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7041323/

A Randomized, Double-Blinded, Placebo-Controlled, Dose ...

This clinical trial evaluated the pharmacokinetics and safety/tolerability of inhaled pirfenidone solution in volunteers and patients with idiopathic pulmonary ...