A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis

Avalyn Pharma

Status and phase: Enrolling; Phase 2

Conditions: Progressive Pulmonary Fibrosis

Treatments: Drug: AP01; Other: Placebo

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT06329401

AP01-007

Details and patient eligibility

About

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

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

300 participants in 3 patient groups, including a placebo group

AP01 High Dose BID

Experimental group

Description:

Pirfenidone Solution for Inhalation

Treatment:

Drug: AP01

AP01 Low Dose BID

Experimental group

Description:

Pirfenidone Solution for Inhalation

Treatment:

Drug: AP01

Placebo BID

Placebo Comparator group

Description:

Placebo solution for inhalation

Treatment:

Other: Placebo