Clinical trial NCT06329401: A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Progressive Pulmonary Fibrosis
Keywords: Chronic-Fibrosing-ILD with progressive phenotype, PF-ILD
Lead sponsor: Avalyn Pharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: DevPro Biopharma
First posted: 2024-03-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
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)
timeFrame: Week 52
Secondary outcomes:
measure: To evaluate the effect of AP01 high dose, AP01 low dose compared to placebo on quality of life (QoL)
timeFrame: 52 weeks
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)
timeFrame: 52 weeks
measure: To evaluate the change from baseline in quantitative lung fibrosis score.
timeFrame: 52 weeks
Other outcomes:
measure: To evaluate the safety of AP01 high dose and AP01 low dose compared to placebo
timeFrame: 52 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Newport Native MD, Inc.
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research - Redding
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Farmington
country: United States
facility: UCONN Health
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Leesburg
country: United States
facility: Clinical Site Partners, LCC
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Pensacola
country: United States
facility: SEC Clinical Research
state: Florida
city: Winter Park
country: United States
facility: Clinical Site Partners
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Evanston
country: United States
facility: Endeavor Health
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Hannibal
country: United States
facility: Hannibal Regional Healthcare System
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mount Kisco
country: United States
facility: Northwell Health - Mount Kisco
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weill Cornell
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greensboro
country: United States
facility: Pulmonix
state: North Carolina
city: Statesville
country: United States
facility: Piedmont HealthCare, PA
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Bend
country: United States
facility: Summit Health
state: Oregon
city: Portland
country: United States
facility: The Oregon Clinic Pulmonary East
state: Oregon
city: Portland
country: United States
facility: The Oregon Clinic Pulmonary West
state: Oregon
city: Hershey
country: United States
facility: The Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Lowcountry Lung and Critical Care
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Franklin
country: United States
facility: Clinical Trials Center of Middle Tennessee
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Lung Institute
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute, Baylor University Medical Center
state: Texas
city: El Paso
country: United States
facility: El Paso Pulmonary Association
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonary and Sleep Center, PA
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Falls Church
country: United States
facility: Inova Healthcare
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Buenos Aires
country: Argentina
facility: Fundacion Respirar
city: Buenos Aires
country: Argentina
facility: CINME
city: Córdoba
country: Argentina
facility: Instituto de Medicina Respiratoria
city: Tucumán
country: Argentina
facility: CIMER Centro Integral de Medicina Respiratoria
city: Tucumán
country: Argentina
facility: Investigaciones En Patologias Respiratorias
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Lung & Sleep
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University Clinical Trials Unit
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
state: Perth West Australia
city: Footscray
country: Australia
facility: Lung Research Victoria
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Ajax
country: Canada
facility: Dynamic Drug Advancement
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Montreal
country: Canada
facility: Research Institute McGill University Health Center
state: Quebec
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
state: Quebec
city: Trois-Rivières
country: Canada
facility: CIC Mauricie
state: Quebec
city: Rennes
country: France
facility: CHU de Rennes
state: Cedex NA
city: Tours
country: France
facility: CHU Tours
state: Indre et Loire
city: Metz
country: France
facility: Robert Schuman Hospital UNEOS
state: Lorraine
city: Angers
country: France
facility: CHU Angers
city: Lyon
country: France
facility: Louis Pradel Hospital
city: Montpellier
country: France
facility: University of Montpellier
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Muenchen
country: Germany
facility: Pneumologisches Studienzentrum München-West
state: Bavaria
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
state: Bavaria
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Lower Saxony
city: Frankfurt
country: Germany
facility: Studienzentrum Dr. Claus Keller
state: Main Hessia
city: Essen
country: Germany
facility: Ruhrlandklinik Essen, Klinik fuer Pneumologie
state: Northrhine westphalia
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz - Zentrum für Thoraxerkrankungen
state: Rhineland-Palatinate
city: Leipzig
country: Germany
facility: Uniklinikum Leipzig Medizinische Klinik II - Bereich
state: Saxony
city: Torrette
country: Italy
facility: A.O.U. delle Marche - Ospedale di Torrette
state: Ancona
city: Venezia
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina
state: Giulia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia
state: Lombardia
city: Rozzano
country: Italy
facility: HUMANITAS Research Hospital
state: Milano
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna - Policlinico Sant' Orsola
state: Romagna
city: Catania
country: Italy
facility: A.O.U. Policlinico G. Rodolico
state: Sicilia
city: Milano
country: Italy
facility: Ospedale San Giuseppe
city: Christchurch
country: New Zealand
facility: Health New Zealand
state: Canterbury
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
state: Dunedine
city: Tauranga
country: New Zealand
facility: Bay of Plenty Clinical School
state: South Tauranga
city: Auckland
country: New Zealand
facility: Greenlane Clinical Centre
city: Bydgoszcz
country: Poland
facility: Vitamed Galaj I Cichomski sp.j.
state: Bydgoszc
city: Lodz
country: Poland
facility: AppleTreeClinics Network
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
state: Andalucía
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Barcelona
country: Spain
facility: Hospital de Sant Pau y la Santa Creu
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar - Leon-Jimenez
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Bornova
country: Turkey
facility: Ege University Medical Faculty Hospital
state: Izmir
city: Cottingham
country: United Kingdom
facility: Hull University Teaching Hospital NHS Trust
state: East Yorkshire
city: Glenfield
country: United Kingdom
facility: Leicester Biomedical Research Centre - Respiratory Theme
state: Leicester
city: Exeter
country: United Kingdom
facility: Royal Devon
state: South West
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Trust, New Cross Hospital, Research and Development
state: West Midlands
city: Leeds
country: United Kingdom
facility: St James University Hospital - LTHT
state: West Yorkshire
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
Study officials:
affiliation: Avalyn Pharma Inc.
name: Avalyn Pharma, Inc.
role: STUDY_DIRECTOR
References:
citation: West A, Chaudhuri N, Barczyk A, Wilsher ML, Hopkins P, Glaspole I, Corte TJ, Sterclova M, Veale A, Jassem E, Wijsenbeek MS, Grainge C, Piotrowski W, Raghu G, Shaffer ML, Nair D, Freeman L, Otto K, Montgomery AB. Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial. Thorax. 2023 Sep;78(9):882-889. doi: 10.1136/thorax-2022-219391. Epub 2023 Mar 22.