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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Avalyn Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Sep 2024 → ongoing

Decision date (initial)

2025-07-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508429-29-00

ClinicalTrials.gov

NCT06329401

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacokinetic

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

Secondary objectives 3

1. To evaluate the effect of AP01 100 mg BID and AP01 50 mg BID compared to placebo on quality of life (QoL) over 52 weeks
2. To evaluate the effect of AP01 compared to placebo on disease progression from Baseline to Week 52
3. To evaluate the effect of AP01 compared to placebo on radiologic measures of lung fibrosis from Baseline to 52 weeks

Conditions and MedDRA coding

Progressive Pulmonary Fibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Able to understand and sign a written informed consent form (ICF) consistent with International Council for Harmonisation (ICH) Guideline for Good Clinical Practice (GCP) and local laws prior to study enrollment.
2. Able to understand the importance of adherence to study drug and the study protocol and willing to follow all study requirements, including the concomitant medication restrictions, throughout the study.
3. Male or female at least 18 years of age at Screening.
4. Subject meets criteria for PPF (modified from Flaherty et al, 2019), 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): a. Relative decline in FVC ≥10% predicted within the previous 24 months based on documented historical spirometry assessments b. 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: o Increased extent or severity of traction bronchiectasis and bronchiolectasis o New ground-glass opacity with traction bronchiectasis o New fine reticulation o Increased extent or increased coarseness of reticular abnormality o New or increased honeycombing o Increased lobar volume loss c. 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 as indicated in criterion 4b above

Exclusion criteria 7

1. Current treatment with oral pirfenidone or nerandomilast at the 9 mg twice daily dose or treatment with oral pirfenidone within 3 months prior to Screening.
2. 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
3. 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.
4. 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.
5. Greater extent of emphysema than of fibrotic ILD on HRCT. Note: CT results must be confirmed through the central over read process.
6. Significant clinical worsening of PPF between Screening Visit 1 and Visit 3 (Week 0/Day 1/Randomization), as assessed by the Investigator.
7. History of acute respiratory exacerbation requiring hospitalization within 12 weeks prior to Screening or at any time during the Screening Period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 3

1. Change from Baseline in QoL measurements as assessed by Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score at Week 52
2. Time to disease progression. Disease progression is defined as absolute FVC percent predicted decline of ≥10% through Week 52 or all-cause death
3. Change in lung fibrosis score based on high-resolution computed tomography (HRCT) from Baseline to 52 weeks

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Avalyn Pharma Inc.

Sponsor organisation

Avalyn Pharma Inc.

Address

701 Pike Street Suite 1500

City

Seattle

Postcode

98101-3926

Country

United States

Scientific contact point

Organisation

Avalyn Pharma Inc.

Contact name

Craig S. Conoscenti

Public contact point

Organisation

Avalyn Pharma Inc.

Contact name

Craig S. Conoscenti

Third parties 12

Locations

7 EU/EEA countries · 44 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 113 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications