A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
- Registration Number
- NCT06329401
- Lead Sponsor
- Avalyn Pharma Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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:
- FVC ≥45% of predicted normal at Screening Visit 1,
- Forced expiratory volume at 1 second (FEV1)/FVC ≥0.7 at Screening Visit 1,
- Diffusing capacity of lung for carbon monoxide (DLCO) ≥30% of predicted, corrected for hemoglobin at Screening Visit 1,
- 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.
-
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:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ˃ 3 times the upper limit of normal (ULN)
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo BID Placebo Placebo solution for inhalation AP01 High Dose BID AP01 Pirfenidone Solution for Inhalation AP01 Low Dose BID AP01 Pirfenidone Solution for Inhalation
- Primary Outcome Measures
Name Time Method 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) Week 52 Change from baseline in forced vital capacity (FVC) (mL)
- Secondary Outcome Measures
Name Time Method To evaluate the effect of AP01 high dose, AP01 low dose compared to placebo on quality of life (QoL) 52 weeks 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.
To evaluate the change from baseline in quantitative lung fibrosis score. 52 weeks Change in lung fibrosis score.
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) 52 weeks Time to disease progression
Trial Locations
- Locations (118)
Instituto de Medicina Respiratoria
🇦🇷Córdoba, Argentina
CIMER Centro Integral de Medicina Respiratoria
🇦🇷Tucumán, Argentina
Investigaciones En Patologias Respiratorias
🇦🇷Tucumán, Argentina
Nepean Lung & Sleep
🇦🇺Kingswood, New South Wales, Australia
Dynamic Drug Advancement
🇨🇦Ajax, Ontario, Canada
CIC Mauricie
🇨🇦Trois-Rivières, Quebec, Canada
CHU de Rennes
🇫🇷Rennes, Cedex NA, France
CHU Tours
🇫🇷Tours, Indre et Loire, France
Robert Schuman Hospital UNEOS
🇫🇷Metz, Lorraine, France
CHU Angers
🇫🇷Angers, France
Louis Pradel Hospital
🇫🇷Lyon, France
University of Montpellier
🇫🇷Montpellier, France
Hôpital Haut-Lévêque
🇫🇷Pessac, France
RoMed Klinikum Rosenheim
🇩🇪Rosenheim, Bavaria, Germany
A.O.U. delle Marche - Ospedale di Torrette
🇮🇹Torrette, Ancona, Italy
A.O.U. Policlinico G. Rodolico
🇮🇹Catania, Sicilia, Italy
Ospedale San Giuseppe
🇮🇹Milano, Italy
SEC Clinical Research
🇺🇸Pensacola, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Pulmonary Associates, PA
🇺🇸Phoenix, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars-Sinai
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Newport Native MD, Inc.
🇺🇸Newport Beach, California, United States
Paradigm Clinical Research - Redding
🇺🇸Redding, California, United States
University of Colorado, Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
UCONN Health
🇺🇸Farmington, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Clinical Site Partners, LCC
🇺🇸Leesburg, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Central Florida Pulmonary Group
🇺🇸Orlando, Florida, United States
Clinical Site Partners
🇺🇸Winter Park, Florida, United States
Piedmont Healthcare, Inc.
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Endeavor Health
🇺🇸Evanston, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Hannibal Regional Healthcare System
🇺🇸Hannibal, Missouri, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Northwell Health - Mount Kisco
🇺🇸Mount Kisco, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Weill Cornell
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Pulmonix
🇺🇸Greensboro, North Carolina, United States
Piedmont HealthCare, PA
🇺🇸Statesville, North Carolina, United States
Accellacare
🇺🇸Wilmington, North Carolina, United States
Southeastern Research Center
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Summit Health
🇺🇸Bend, Oregon, United States
The Oregon Clinic Pulmonary East
🇺🇸Portland, Oregon, United States
The Oregon Clinic Pulmonary West
🇺🇸Portland, Oregon, United States
The Pennsylvania State University
🇺🇸Hershey, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
Lowcountry Lung and Critical Care
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Clinical Trials Center of Middle Tennessee
🇺🇸Franklin, Tennessee, United States
Vanderbilt Lung Institute
🇺🇸Nashville, Tennessee, United States
Baylor Scott & White Research Institute, Baylor University Medical Center
🇺🇸Dallas, Texas, United States
El Paso Pulmonary Association
🇺🇸El Paso, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center
🇺🇸Houston, Texas, United States
Metroplex Pulmonary and Sleep Center, PA
🇺🇸McKinney, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
Inova Healthcare
🇺🇸Falls Church, Virginia, United States
University of Washington
🇺🇸Seattle, Washington, United States
Fundacion Respirar
🇦🇷Buenos Aires, Argentina
CINME
🇦🇷Buenos Aires, Argentina
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
John Hunter Hospital
🇦🇺New Lambton, New South Wales, Australia
Macquarie University Clinical Trials Unit
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Institute for Respiratory Health
🇦🇺Nedlands, Perth West Australia, Australia
Lung Research Victoria
🇦🇺Footscray, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
St. Joseph's Healthcare Hamilton
🇨🇦Hamilton, Ontario, Canada
Research Institute McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
🇨🇦Québec, Quebec, Canada
Pneumologisches Studienzentrum München-West
🇩🇪Muenchen, Bavaria, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Lower Saxony, Germany
Studienzentrum Dr. Claus Keller
🇩🇪Frankfurt, Main Hessia, Germany
Ruhrlandklinik Essen, Klinik fuer Pneumologie
🇩🇪Essen, Northrhine westphalia, Germany
Universitätsmedizin Mainz - Zentrum für Thoraxerkrankungen
🇩🇪Mainz, Rhineland-Palatinate, Germany
Uniklinikum Leipzig Medizinische Klinik II - Bereich
🇩🇪Leipzig, Saxony, Germany
Azienda Sanitaria Universitaria Giuliano Isontina
🇮🇹Venezia, Giulia, Italy
Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia
🇮🇹Pavia, Lombardia, Italy
HUMANITAS Research Hospital
🇮🇹Rozzano, Milano, Italy
IRCCS AOU di Bologna - Policlinico Sant' Orsola
🇮🇹Bologna, Romagna, Italy
Health New Zealand
🇳🇿Christchurch, Canterbury, New Zealand
Dunedin Hospital
🇳🇿Dunedin, Dunedine, New Zealand
Bay of Plenty Clinical School
🇳🇿Tauranga, South Tauranga, New Zealand
Greenlane Clinical Centre
🇳🇿Auckland, New Zealand
Vitamed Galaj I Cichomski sp.j.
🇵🇱Bydgoszcz, Bydgoszc, Poland
AppleTreeClinics Network
🇵🇱Lodz, Poland
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Andalucía, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital de Sant Pau y la Santa Creu
🇪🇸Barcelona, Spain
Hospital Universitario Puerta del Mar - Leon-Jimenez
🇪🇸Cadiz, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Ege University Medical Faculty Hospital
🇹🇷Bornova, Izmir, Turkey
Hull University Teaching Hospital NHS Trust
🇬🇧Cottingham, East Yorkshire, United Kingdom
Leicester Biomedical Research Centre - Respiratory Theme
🇬🇧Glenfield, Leicester, United Kingdom
Royal Devon
🇬🇧Exeter, South West, United Kingdom
The Royal Wolverhampton NHS Trust, New Cross Hospital, Research and Development
🇬🇧Wolverhampton, West Midlands, United Kingdom
St James University Hospital - LTHT
🇬🇧Leeds, West Yorkshire, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom