RecruitingPhase 2NCT06329401

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

A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study Evaluating the Safety and Efficacy of Pirfenidone Solution for Inhalation (AP01) in Participants With PPF


Sponsor

Avalyn Pharma Inc.

Enrollment

375 participants

Start Date

Apr 3, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria17

  • 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):
  • Relative decline in FVC ≥10% predicted within the previous 24 months based on documented historical spirometry assessments
  • Relative decline in FVC ≥5% to \<10% predicted within the previous 24 months based on documented historical spirometry assessments 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 (from historical HRCT taken up to 24 months prior to Screening Visit 1), 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
  • 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 Criteria9

  • 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 \>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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Interventions

DRUGAP01

Oral inhalation solution

OTHERPlacebo

Placebo oral inhalation solution


Locations(152)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Mayo Clinic- Scottsdale

Scottsdale, 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 California - San Francisco

San Francisco, 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

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

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

Montefiore Medical Center

The Bronx, New York, United States

Duke University

Durham, 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

Cleveland Clinic

Cleveland, 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

UT Southwestern 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, Buenos Aires, Argentina

CINME

Buenos Aires, Buenos Aires, Argentina

Hospital Italiano de Buenos Aires

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto Ave Pulmo, Fundacion Enfisema

Mar del Plata, Buenos Aires, Argentina

Clinica Monte Grande

Monte Grande, Buenos Aires, Argentina

Centro Respiratorio Quilmes

Quilmes, Buenos Aires, Argentina

Instituto de Medicina Respiratoria

Córdoba, Córdoba Province, Argentina

CIMER Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province, Argentina

Investigaciones En Patologias Respiratorias

San Miguel de Tucumán, Tucumán Province, Argentina

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Nepean Lung & Sleep

Kingswood, 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

Wallace Street Specialist Centre/Lung Research QLD Pty Ltd

Brisbane, Queensland, Australia

Lung Research Victoria

Footscray, Victoria, Australia

Alfred Health

Melbourne, Victoria, Australia

Canberra Hospital

Canberra, Australia

UZ Leuven

Leuven, Belgium

CHU de Liège

Liège, Belgium

Vancouver General Hospital

Vancouver, British Columbia, Canada

Dynamic Drug Advancement

Ajax, Ontario, 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

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

Louis Pradel Hospital

Lyon, Lyon, France

University of Montpellier

Montpellier, Montpellier, France

CHU Angers

Angers, France

APHP - Hopital Bicetre

Le Kremlin-Bicêtre, France

Hôpital Paris St Jozeph

Paris, France

Hôpital Haut-Lévêque

Pessac, France

Pneumologisches Studienzentrum München-West

Munich, Bavaria, Germany

Muenchen Klinik Bogenhausen - Klinik für Pneumologie und Pneumologische Onkologie

München, Bavaria, Germany

RoMed Klinikum Rosenheim

Rosenheim, Bavaria, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Studienzentrum Dr. Claus Keller

Frankfurt, Main Hessia, Germany

Ruhrlandklinik Essen, Klinik fuer Pneumologie

Essen, North Rhine-Westphalia, Germany

Universitätsmedizin Mainz - Zentrum für Thoraxerkrankungen

Mainz, Rhineland-Palatinate, Germany

Uniklinikum Leipzig Medizinische Klinik II - Bereich

Leipzig, Saxony, Germany

Vivantes Klinikum Neukölln - Klinik für Innere Medizin - Pneumologie und Infektiologie

Berlin, State of Berlin, Germany

A.O.U. delle Marche - Ospedale di Torrette

Torrette, Ancona, Italy

Azienda Ospedaliera dei Colli - Ospedale Monaldi

Naples, Campania, Italy

Università degli Studi di Napoli Federico II - Ospedale Monaldi

Naples, Campania, Italy

IRCCS AOU di Bologna - Policlinico Sant' Orsola

Bologna, Emilia-Romagna, Italy

Azienda Sanitaria Universitaria Giuliano Isontina

Venezia, Giulia, Italy

Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia

Pavia, Lombardy, Italy

Ospedale San Giuseppe

Milan, Milano, Italy

HUMANITAS Research Hospital

Rozzano, Milano, Italy

A.O.U. Policlinico G. Rodolico

Catania, Sicily, Italy

St Antoniusziekenhuis

Nieuwegein, Utrecht, Netherlands

Erasmus University Medical Center

Rotterdam, Netherlands

Greenlane Clinical Centre

Auckland, Auckland, New Zealand

Health New Zealand

Christchurch, Canterbury, New Zealand

Dunedin Hospital

Dunedin, Dunedine, New Zealand

Bay of Plenty Clinical School

Tauranga, South Tauranga, New Zealand

Vitamed Galaj I Cichomski sp.j.

Bydgoszcz, Bydgoszc, Poland

University Hospital in Krakow

Krakow, Krakow, Poland

Department of Pneumology of the University Hospital No 1

Lodz, Poland

PRYWATNY GABINET LEKARSKI GINEKOLOGIA I POŁOZNICTWO ULTRASONOGRAFIA Prof. Dr hab. Med. Jacek Suzin

Lodz, Poland

AppleTreeClinics Network

Lodz, Łódź Voivodeship, Poland

Hospital Universitario Virgen de las Nieves

Granada, Andalusia, Spain

Hospital de Sant Pau y la Santa Creu

Barcelona, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital Gregorio Marañon

Madrid, Madrid, Spain

Hospital Universitario Ramon y Cajal

Madrid, Madrid, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Universitario Virgen del Rocío

Seville, Sevilla, Spain

Hospital Universitary de Bellvitge

Barcelona, Spain

Hospital Universitario Puerta del Mar - Leon-Jimenez

Cadiz, Spain

Ege University Medical Faculty Hospital

Bornova, İzmir, Turkey (Türkiye)

Cukurova University Medical Faculty

Adana, Turkey (Türkiye)

Health Sciences University, Gulhane Faculty of Medicine

Ankara, Turkey (Türkiye)

Hull University Teaching Hospital NHS Trust

Cottingham, East Yorkshire, United Kingdom

Birmingham Heartlands Hospital

Birmingham, Heartlands, United Kingdom

Leicester Biomedical Research Centre - Respiratory Theme

Glenfield, Leicester, United Kingdom

St George's University Hospitals NHS Foundation Trust

London, London, United Kingdom

ILD Unit, University Hospitals Birmingham NHS Foundation Trust Theme

Birmingham, Midlands, United Kingdom

C-TRIC Altnagelvin Hospital

Londonderry, Northern Ireland, United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, Oxon, 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

Royal Papworth Hospital

Cambridge, United Kingdom

Royal Brompton Hospital

London, United Kingdom

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Nottingham University NHS Trust

Nottingham, United Kingdom

University Hospitals of North Midlands NHS Trust, Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

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NCT06329401


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