A Study Evaluating the Safety and Efficacy of AP01 in Participants With Progressive Pulmonary Fibrosis (PPF)

A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study Evaluating the Safety and Efficacy of Pirfenidone Solution for Inhalation (AP01) in Participants With PPF

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

Study Overview

• Status: Recruiting
• Conditions: Progressive Pulmonary Fibrosis
• Intervention / Treatment: Drug: AP01; Other: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of 2 doses of AP01 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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Craig S. Conoscenti, MD; Phone Number: 206-707-0304; Email: cconoscenti@avalynpharma.com
• Study Contact Backup: Name: Daniele Tompkins; Phone Number: 205 973-983-3700; Email: dtompkins@devprobiopharma.com

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Newport Native MD, Inc.
    • Redding, California, United States, 96001
      • Not yet recruiting
      • Paradigm Clinical Research - Redding
  • Florida
    • Leesburg, Florida, United States, 34748
      • Not yet recruiting
      • Clinical Site Partners, LCC
    • Ocala, Florida, United States, 34470
      • Not yet recruiting
      • Renstar Medical Research
    • Winter Park, Florida, United States, 32789
      • Not yet recruiting
      • Clinical Site Partners
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Recruiting
      • Accellacare
    • Winston-Salem, North Carolina, United States, 27103
      • Not yet recruiting
      • Southeastern Research Center
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Recruiting
      • Lowcountry Lung and Critical Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant meets criteria for PPF, as follows:
• In participants with ILD of known or unknown etiology other than IPF who have radiological evidence of pulmonary fibrosis, PPF is defined as:

I. Physiological evidence of disease progression:

a. Absolute decline in FVC ≥5% predicted within the previous 6 to 12 months relative to Screening Visit 1

And at least 1 of the following 2 criteria occurring within the past year with no alternative explanation:

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

III. Radiological evidence of disease progression (one or more of the following):

a. Increased extent or severity of traction bronchiectasis and bronchiolectasis b. New ground-glass opacity with traction bronchiectasis c. New fine reticulation d. Increased extent or increased coarseness of reticular abnormality e. New or increased honeycombing f. Increased lobar volume loss

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

  1. FVC ≥45% of predicted normal at Screening Visit 1,
  2. Forced expiratory volume at 1 second (FEV1)/FVC ≥0.7 at Screening Visit 1,
  3. Diffusing capacity of lung for carbon monoxide (DLCO) ≥30% of predicted, corrected for hemoglobin at Screening Visit 1,
  4. Acceptability: Participants can perform acceptable spirometry (i.e., meet American Thoracic Society (ATS)/ European Respiratory Society (ERS) acceptability criteria at both Screening Visits).
• For participants already on nintedanib (up to 30% of participants): Must have been on nintedanib for 6 to 12 months prior to Screening and have met criteria for PPF while on nintedanib for the same period in which the ≥5% decline in FVC was observed. Must have had no change in nintedanib dose for at least 12 weeks prior to Screening. For participants 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 > 1.5 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AP01 High Dose BID; Pirfenidone Solution for Inhalation	Drug: AP01; Oral inhalation solution; Other Names: Pirfenidone Solution
Experimental: AP01 Low Dose BID; Pirfenidone Solution for Inhalation	Drug: AP01; Oral inhalation solution; Other Names: Pirfenidone Solution
Placebo Comparator: Placebo BID; Placebo solution for inhalation	Other: Placebo; Placebo oral inhalation solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of AP01 high dose twice a day (BID) or AP01 low dose twice a day (BID) compared to placebo twice a day (BID)	Change from baseline in forced vital capacity (FVC) (mL)	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Time to disease progression	52 weeks
To evaluate the effect of AP01 high dose, AP01 low dose compared to placebo on quality of life (QoL)	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.	52 weeks
To evaluate the change from baseline in quantitative lung fibrosis score.	Change in lung fibrosis score.	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of AP01 high dose and AP01 low dose compared to placebo	Incidents of adverse events (AEs), serious adverse events (SAEs), and treatment-emergent deaths	52 weeks

Collaborators and Investigators

• Sponsor: Avalyn Pharma Inc.
• Collaborators: DevPro Biopharma
• Investigators: Study Director: Avalyn Pharma, Inc., Avalyn Pharma Inc.

Publications and helpful links

General Publications

• West A, Chaudhuri N, Barczyk A, Wilsher ML, Hopkins P, Glaspole I, Corte TJ, Sterclova M, Veale A, Jassem E, Wijsenbeek MS, Grainge C, Piotrowski W, Raghu G, Shaffer ML, Nair D, Freeman L, Otto K, Montgomery AB. Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial. Thorax. 2023 Sep;78(9):882-889. doi: 10.1136/thorax-2022-219391. Epub 2023 Mar 22.

Helpful Links

• Content

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Chronic-Fibrosing-ILD with progressive phenotype, PF-ILD
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: AP01-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No