Brief Summary
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.
Brief Title
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Detailed 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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
206-707-0304
Central Contact Email
cconoscenti@avalynpharma.com
Central Contact Role
Contact
Central Contact Phone
973-983-3700
Central Contact Phone Ext
205
Central Contact Email
dtompkins@devprobiopharma.com
Completion Date
Completion Date Type
Estimated
Conditions
Progressive Pulmonary Fibrosis
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Chronic-Fibrosing-ILD with progressive phenotype, PF-ILD
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06329401
Org Class
Industry
Org Full Name
Avalyn Pharma Inc.
Org Study Id
AP01-007
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study Evaluating the Safety and Efficacy of Pirfenidone Solution for Inhalation (AP01) in Participants With PPF
Primary Outcomes
Outcome Description
Change from baseline in forced vital capacity (FVC) (mL)
Outcome Measure
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)
Outcome Time Frame
Week 52
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
52 weeks
Outcome Measure
To evaluate the effect of AP01 high dose, AP01 low dose compared to placebo on quality of life (QoL)
Outcome Description
Time to disease progression
Outcome Time Frame
52 weeks
Outcome Measure
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)
Outcome Description
Change in lung fibrosis score.
Outcome Time Frame
52 weeks
Outcome Measure
To evaluate the change from baseline in quantitative lung fibrosis score.
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ali Mansour
Investigator Email
amansour@montefiore.org