Pirfenidone Solution for Inhalation (AP01) in Progressive Pulmonary Fibrosis

What is the Purpose of this Study?

The purpose of this study is to evaluate the safety and effectiveness of multiple doses of an experimental drug called AP01 compared with placebo (inactive substance) in people who have progressive pulmonary fibrosis (PPF). The study will also evaluate how AP01 behaves inside the body and how it leaves the body (pharmacokinetics); for this reason, blood samples will be collected. AP01 is hypothesized to slow the worsening of lung scarring in PPF. The active component of the study drug (pirfenidone) is approved as treatment for certain types of lung disease when given as a capsule or tablet, but in this study, it is experimental because it will be given as a solution for inhalation using the eFlow Nebulizer System. Participants will be assigned to 1 of 3 groups. The first group will receive 50 mg of AP01; the second group will receive 100 mg of AP01; and the third group will receive placebo. The chance of receiving the study drug is 60%, and the chance of receiving placebo is 40%. Participants will self-administer the AP01 or placebo using the eFlow Nebulizer System. Participants will be assigned to 1 of 3 groups. The first group will receive 50 mg of AP01; the second group will receive 100 mg of AP01; and the third group will receive placebo. The chance of receiving the study drug is 60%, and the chance of receiving placebo is 40%. Participants will self-administer the AP01 or placebo using the eFlow Nebulizer System.

Eligibility

* Participant meets criteria for PPF, 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):

Inclusion Criteria:

* Participant meets criteria for PPF, 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):
1. Relative decline in FVC ≥10% predicted within the previous 24 months compared to Screening Visit 1
2. Relative decline in FVC ≥5 to \<10% predicted within the previous 24 months compared to Screening Visit 1 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, for example:
* Increased extent or severity of traction bronchiectasis and bronchiolectasis
* New ground-glass opacity with traction bronchiectasis
* New fine reticulation
* Increased extent or increased coarseness of reticular abnormality
* New or increased honeycombing
* Increased lobar volume loss
3. 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
* Meeting all of the following criteria during the Screening Period:
a. 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 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).
• For subjects already on nintedanib (up to 30% of subjects): Must have been on nintedanib for at least 6 months prior to Screening with or without dose adjustments and/or drug interruptions during that period. For subjects 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 \>2.0 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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study Evaluating the Safety and Efficacy of Pirfenidone Solution for Inhalation in Subjects with Progressive Pulmonary Fibrosis

Study Details

Disease Type/Condition

Other

Principal Investigator

Zaman, Tanzira

Age Group

Adult

Phase

IRB Number

STUDY00003327

ClinicalTrials.gov ID

NCT06329401

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org