A Placebo-Controlled Study of Inhaled Pirfenidone in Progressive Pulmonary Fibrosis

Phase 2

Recruiting

• Conditions: Progressive Pulmonary Fibrosis

• Registration Number: 2023-508429-29-00
• Lead Sponsor: Avalyn Pharma Inc.

Brief Summary

To evaluate the effect of AP01 compared to AP01 placebo (hereafter referred to as placebo) on lung function over 52 weeks in subjects with PPF

Detailed Description

This is a randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of 2 doses of AP01 (pirfenidone solution for inhalation) versus placebo on top of standard of care in participants with PPF over 52 weeks. Up to 300 eligible participants will be randomized to 1 of 3 treatment arms: AP01 high dose, AP01 low dose, or placebo.

Study Timeline

• Study First Submitted: 2024-03-12
• Study First Submitted QC: 2024-03-19
• Study First Posted: 2024-03-25
• Study Start: 2024-04-03
• Status Verified: 2025-11
• Last Update Submitted: 2025-11-18
• Last Update Posted: 2025-11-21
• Primary Completion: 2027-06
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 375

Inclusion Criteria

• Participant meets criteria for PPF, as follows:
• In subjects with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF) who have radiological evidence of pulmonary fibrosis, PPF is defined as:

Physiological evidence of disease progression with at least 1 of the following criteria despite treatment with approved or unapproved medications commonly used in practice (per Investigator):

1. Relative decline in FVC ≥10% predicted within the previous 24 months based on documented historical spirometry assessments

2. Relative decline in FVC ≥5% to <10% predicted within the previous 24 months based on documented historical spirometry assessments with at least 1 of the 2 following criteria:

   • Worsening respiratory symptoms (Note: Changes attributable to comorbidities e.g., infection, heart failure must be excluded) OR

   • Radiological (HRCT) evidence of disease progression per a local or central radiologist (from historical HRCT taken up to 24 months prior to Screening Visit 1), for example:

     • Increased extent or severity of traction bronchiectasis and bronchiolectasis
     • New ground-glass opacity with traction bronchiectasis
     • New fine reticulation
     • Increased extent or increased coarseness of reticular abnormality
     • New or increased honeycombing
     • Increased lobar volume loss

3. Worsening of respiratory symptoms (Note: Changes attributable to comorbidities e.g., infection, heart failure must be excluded) AND radiological (HRCT) evidence of disease progression per a local or central radiologist

   • Meeting all of the following criteria during the Screening Period:

a. FVC ≥45% of predicted normal at Screening Visit 1, b. Forced expiratory volume at 1 second (FEV1)/FVC ≥0.7 or ≥age-adjusted lower limit of normal at Screening Visit 1, c. Diffusing capacity of lung for carbon monoxide (DLCO) ≥30% of predicted, corrected for hemoglobin at Screening Visit 1, d. Acceptability: Participants can perform acceptable spirometry (i.e., meet American Thoracic Society (ATS)/ European Respiratory Society (ERS) acceptability criteria at both Screening Visits).

• For subjects already on nintedanib (up to 30% of subjects): Must have been on nintedanib for at least 6 months prior to Screening with or without dose adjustments and/or drug interruptions during that period. For subjects who have discontinued nintedanib prior to Screening: Must have been off of nintedanib for a minimum of 12 weeks.

Exclusion Criteria

• Current treatment with oral pirfenidone or treatment with oral pirfenidone within 3 months prior to Screening.

• Elevated liver enzymes and liver injury at Screening defined as:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ˃ 3 times the upper limit of normal (ULN)
  2. Bilirubin >2.0 x ULN

• Renal disease with a creatinine clearance < 30 mL/min, calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula. Retesting is allowed once.

• Diagnosis of idiopathic pulmonary fibrosis (IPF) based on the ATS diagnostic algorithm for IPF. UIP that is not idiopathic, for example related to rheumatoid arthritis (RA), familial interstitial lung disease (ILD), or other is not exclusionary.

• Greater extent of emphysema than of fibrotic ILD on HRCT. Note: CT results must be confirmed through the central over read process.

• Significant clinical worsening of PPF between Screening

• Participants who cannot meet protocol-specified Baseline stability criteria. FVC Baseline stability is defined as the FVC assessments at Visit 3 being within ±12% of the mean of the FVC assessments obtained at the 2 preceding visits. At Visit 3, if the pre-dose FVC is outside of ±12% range, the participant will not be randomized and will be considered a screen failure.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The main trial endpoint is the change from baseline in FVC, the maximum amount of air that can be exhaled when blowing out as fast as possible (measured in milliliters) at Week 52		The main trial endpoint is the change from baseline in FVC, the maximum amount of air that can be exhaled when blowing out as fast as possible (measured in milliliters) at Week 52

Secondary Outcome Measures

Name	Time	Method
To evaluate the effect of AP01 high dose and AP01 low dose compared to placebo on disease progression (defined as absolute FVC percent predicted decline of ≥10% prior to Week 52)	52 weeks	Time to disease progression
To evaluate the effect of AP01 high dose, AP01 low dose compared to placebo on quality of life (QoL)	52 weeks	Absolute change from Baseline in QoL measurements as assessed by Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score. The L-PF is a 44-item questionnaire to assess how impacted a participant is by disease symptoms on a scale from 0 (Not at all) to 4 (Extremely). The higher the summary score, the greater the impairment.
To evaluate the change from baseline in quantitative lung fibrosis score.	52 weeks	Change in lung fibrosis score.

Trial Locations

Locations (146)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Pulmonary Associates, PA; 🇺🇸 Phoenix, Arizona, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai; 🇺🇸 Los Angeles, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Newport Native MD, Inc.; 🇺🇸 Newport Beach, California, United States

Paradigm Clinical Research - Redding; 🇺🇸 Redding, California, United States

University of Colorado, Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

UCONN Health; 🇺🇸 Farmington, Connecticut, United States

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