A Placebo-Controlled Study of Inhaled Pirfenidone in 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.
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 141
Male or female at least 18 years of age at Screening.
Subject meets criteria for PPF (modified from Flaherty et al, 2019) (see full description in the protocol)
Meeting all of the following criteria during the Screening Period: a. Forced vital capacity (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 Global Lung Function Initiative (GLI) values (Quanjer et al, 2012) 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). Note: Spirometry (including DLCO) obtained at Visit 1 may be repeated to confirm eligibility once, if discussed and approved by the Medical Monitor (e.g., technical issue, subject fatigue).
For participants already on nintedanib (up to 30% of participants): Must have been on nintedanib for 6 months prior to Screening with or without dose adjustments and/or drug interruptions during that period. For participants who have discontinued nintedanib prior to Screening: Must have been off of nintedanib for a minimum of 12 weeks.
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: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ˃3 times the upper limit of normal (ULN), OR b. Bilirubin >2.0 x ULN
Renal disease with a creatinine clearance <30 mL/min, calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula (Inker et al, 2021). Retesting is allowed once.
Diagnosis of idiopathic pulmonary fibrosis (IPF) based on the ATS diagnostic algorithm for IPF. Usual interstitial pneumonia (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 Visit 1 and Visit 3 (Week 0/Day 1/Randomization), as assessed by the Investigator.
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
- Arm && Interventions
Group Intervention Description Placebo BID Placebo Placebo solution for inhalation AP01 High Dose BID AP01 Pirfenidone Solution for Inhalation AP01 Low Dose BID AP01 Pirfenidone Solution for Inhalation
- 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 Absolute change from Baseline in QoL measurements as assessed by Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score at Week 52 Absolute change from Baseline in QoL measurements as assessed by Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score at Week 52
Time to disease progression. Disease progression is defined as absolute FVC percent predicted decline of ≥10% prior to Week 52 Time to disease progression. Disease progression is defined as absolute FVC percent predicted decline of ≥10% prior to Week 52
Change in lung fibrosis score based on high-resolution computed tomography (HRCT) from Baseline to 52 weeks Change in lung fibrosis score based on high-resolution computed tomography (HRCT) from Baseline to 52 weeks
Trial Locations
- Locations (41)
Muenchen Klinik gGmbH
🇩🇪Munich, Germany
Universitaet Leipzig
🇩🇪Leipzig, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum Am Universitaetsklinikum Essen gGmbH
🇩🇪Essen, Germany
Vivantes Netzwerk fuer Gesundheit GmbH
🇩🇪Berlin, Germany
Romed Klinikum Rosenheim
🇩🇪Rosenheim, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
🇩🇪Mainz, Germany
Pneumological Study Center Munich West
🇩🇪Munich, Germany
Humanitas Mirasole S.p.A.
🇮🇹Rozzano, Italy
Azienda Ospedaliero Universitaria Delle Marche
🇮🇹Ancona, Italy
Multimedica S.p.A.
🇮🇹Milan, Italy
Scroll for more (31 remaining)Muenchen Klinik gGmbH🇩🇪Munich, GermanyPeter SchrammSite contact+498992704316peter.schramm@muenchen-klinik.de