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. Male or female at least 18 years of age at Screening.
2. Subject meets criteria for PPF (modified from Flaherty et al, 2019) (see full description in the protocol)
3. 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).
4. For participants already on nintedanib (up to 30% of participants): Must have been on nintedanib for 12 weeks 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.

Exclusion criteria 7

1. Current treatment with oral pirfenidone 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. 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.

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 11

Locations

7 EU/EEA countries · 45 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 108 files

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

Application history

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