A Study of AV-101 (Dry Powder Inhaled Imatinib) in Patients With Pulmonary Arterial Hypertension (PAH) (IMPAHCT)

IMPAHCT: A Phase 2b/3, Randomized, Double-Blind, Placebo-Controlled, 24-Week Dose Ranging and Confirmatory Study to Evaluate the Safety and Efficacy of AV-101 in Patients With Pulmonary Arterial Hypertension (PAH)

IMPAHCT: Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial is a Phase 2b/Phase 3 study to evaluate the safety and efficacy of AV-101 (dry powder inhaled imatinib) in patients with Pulmonary Arterial Hypertension (PAH). The Phase 2b part of the study will assess three doses to establish an optimal dose for the Phase 3 part of the study. The Phase 2b primary endpoint will be the placebo corrected change in pulmonary vascular resistance (PVR). The Phase 3 primary endpoint will be the placebo corrected change in 6-minute walk distance (6MWD) after 24 weeks of treatment.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: AV-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Sanatorio de la Trinidad Mitre
  • Buenos Aires, Argentina, 1134
    • Hospital Britanico de Buenos Aires
  • Buenos Aires, Argentina, 1425
    • Nexo Salud Investigacion Clinica
  • Caba, Argentina, 1425
    • Cardiología Palermo
  • Córdoba, Argentina, 5009
    • Insituto Medico DAMIC
  • Córdoba, Argentina, X5004FJE
    • Hospital Italiano de Córdoba
  • Santa Fe, Argentina, S300EOZ
    • Hospital Dr. Jose Maria Cullen
• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Murdoch, Australia, 6150
    • Fiona Stanley Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Concord West, New South Wales, Australia, 2138
      • Concord Repatriation General Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Vienna, Austria, 1090
    • AKH - Medizinische Universitat Wien
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme - Cliniques universitaires de Bruxelles
  • Leuven, Belgium, 3000
    • UZ Leuven
• Brazil
  • Porto Alegre, Brazil, 90035-074
    • Santa Casa de Misericordia de Porto Alegre
  • São Paulo, Brazil, 05403
    • Heart Institute - University of São Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • The Governors of the University of Calgary
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Science Centre
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Chile
  • Santiago, Chile, 8330024
    • Centro de Investigaciones Clinicas de la Universidad Catolica
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Chongqing, China, 40016
    • Chongqing Medical University - The First Affiliated Hospital
  • Guangdong, China, 510000
    • Guangdong Provincial People's Hospital
  • Hunan, China, 410011
    • Central South University - The Second Xiangya Hospital
  • Kunming, China, 650051
    • Yanan Hospital of Kunming City
  • Lanzhou, China, 730000
    • Gansu Provincial People's Hospital
  • Nanjing, China, 210009
    • Southeast University (SEU) - Zhongda Hospital
  • Shanghai, China, 200437
    • Shanghai Pulmonary Hospital
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
• Czechia
  • Praha, Czechia, 128 21
    • Vseobecna Fakultni Nemocnice V Praze
• France
  • Bron, France, 69677
    • Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
  • Marseille, France, 94275
    • Hopital Nord - CHU Marseille
  • Montpellier, France, 34295
    • Hopital Arnaud de Villeneuve
  • Strasbourg, France, 67091
    • Les Hôpitaux Universitaires de Strasbourg
  • Cedex
    • Le Kremlin-Bicêtre, Cedex, France, 94275
      • Groupement Hospitalier Sud - Hôpital Bicêtre
• Germany
  • Dresden, Germany, 1307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Giesen, Germany, 35292
    • Universitaetsklinikum Giessen Und Marburg Gmbh Standort Giessen
  • Heidelberg, Germany, 69126
    • Universitaetsklinikum Heidelberg
  • München, Germany, 81925
    • Munchen Klinik Bogenhausen
• Greece
  • Athens, Greece, 10676
    • University General Hospital Attikon
  • Kallithéa, Greece, 17674
    • Cardiosurgery Hospital
  • Thessaloníki, Greece, 54637
    • AHEPA General Hospital of Thessaloniki
• Israel
  • Haifa, Israel, 34362
    • The Lady Davis Carmel Medical Center
  • Jerusalem, Israel, 91999
    • Hadassah University Hospital - Ein Kerem
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Foggia, Italy, 71122
    • Azienda Ospedaliero Universitaria Ospedali Riuniti - Foggia
  • Milan, Italy, 20123
    • Ospedale San Giuseppe - Fatebenefratelli
  • Monza, Italy, 20900
    • Azienda Socio Sanitaria Territoriale Di Monza
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Vincenzo Monaldi
  • Palermo, Italy, 90127
    • Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Rome, Italy, 137
    • Azienda Ospedaliera Universitaria Policlinico Umberto I
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera
  • Monterrey, Mexico, 64460
    • Universidad Autonoma de Nuevo Leon, Hospital Universitario
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • CICUM San Miguel
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Unidad de Investigacion Clinica en Medicina S.C.
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam UMC, locatie VUmc
• Poland
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Poznań, Poland, 61-848
    • Szpital Kliniczny Przemienienia Pańskiego UM im. Marcinkowskiego
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
  • Łódź, Poland, 91-347
    • Bieganski Provincial Specialist Hospital
• Portugal
  • Almada, Portugal, 2805-267
    • Hospital Garcia de Orta, EPE
  • Lisboa, Portugal, 1649-035
    • Hospital Pulido Valente
  • Porto, Portugal, 4099-001
    • CHUPorto
• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • CardioPulmonary Research Center
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
• South Africa
  • Johannesburg, South Africa, 2193
    • Center of Chest Disease Johannesburg
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clínic de Barcelona
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hosp. Universitario Gran Canaria Doctor Negrin
  • Madrid, Spain, 28014
    • Hospital 12 de Octubre
  • Madrid, Spain, 28046
    • Universidad Autonoma de Madrid
  • Málaga, Spain, 29071
    • Hospital Universitario Virgen de la Victoria
  • Salamanca, Spain, 37007
    • Hospital universtario de Salamanca
  • Santander, Spain, 39003
    • Hosp. Universitario Marques de Valdecilla
  • Toledo, Spain, 45007
    • Hospital Universitario de Toledo
• Sweden
  • Umeå, Sweden, 907 37
    • Norrlands Universitetssjukhus
• United Kingdom
  • Glasgow, United Kingdom, G81 4DY
    • Golden Jubilee National Hospital
  • London, United Kingdom, SW3 6HP
    • Royal Brompton Hospital
  • Newcastle, United Kingdom, NE7 7DN
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • England
    • London, England, United Kingdom, W12 0HS
      • Imperial College Healthcare NHS Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists, Ltd.
    • Tucson, Arizona, United States, 85724
      • University of Arizona, Department of Medicine
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90073
      • Dept of Veterans Affairs Greater Los Angeles Healthcare System
    • Los Angeles, California, United States, 90024
      • UCLA/David Geffen School of Medicine-Pulmonary and Criticial Care
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center, Pulmonary & Critical Care
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California
    • Torrance, California, United States, 90509
      • LA Biomedical Research Institute Harbor
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • District of Columbia
    • Washington, District of Columbia, United States, 20073
      • George Washington University Medical Faculty Associates, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Orlando, Florida, United States, 32804
      • Orlando Heart Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center, Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center- Hematology/Oncology Section
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • The Unviersity of New Mexico - UNM Hospitals
  • New York
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian Brooklyn Methodist Hospital
    • New York, New York, United States, 10016
      • NYU Langone Seaport
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center - Duke South Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Center for Research and Education
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical CEnter
  • Oregon
    • Oregon City, Oregon, United States, 97701
      • Bend Memorial Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • Stat Care Pulmonary Consultants, PLLC
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Medical Group - Sentara Pulmonary & Critical Care Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria

• PAH belonging to one of the subgroups:

  1. I/HPAH, PAH-CTD,
  2. PAH due to drugs and/or toxins/chemicals (having been in the care of the investigator for at least one year with no relapses of drug or toxin/chemical abuse),
  3. HIV associated or
  4. PAH due to repaired congenital heart disease (at least 1 year since repair)
• World Health Organization (WHO) Functional Class II, III or IV symptoms
• Stable concomitant background therapy of at least one PAH approved medications
• Able to walk a distance of at least 100 m but no more than 475 m during the Screening 6-minute walk tests.

Key Exclusion Criteria

• Pulmonary hypertension (PH) belonging to Groups 2 to 5
• A history of left-sided heart disease
• Pregnant or breast-feeding females

Additional criteria may apply, per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo administered via dry powder inhalation
Experimental: AV-101 10 mg	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: AV-101 35 mg	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: AV-101 70 mg	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2b: Change from Baseline in Pulmonary Vascular Resistance (PVR)	24 weeks
Phase 3: Change from Baseline in Six Minute Walk Distance (6MWD)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2b: Change from Baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP)		24 weeks
Phase 2b: Change from Baseline in Six Minute Walk Distance (6MWD)		24 weeks
Phase 2b: Proportion of Subjects with Improvement in WHO Functional Class		24 weeks
Phase 2b: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score	REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk	24 weeks
Phase 2b: Change from Baseline in Health-Related Quality of Life emPHasis-10 Questionnaire Score	emPHasis-10 questionnaire scores range from 0 - 50; a higher score represents a higher symptom burden	24 weeks
Phase 3: Change from Baseline in NT-proBNP		24 weeks
Phase 3: Time to Clinical Worsening		24 weeks
Phase 3: Proportion of Subjects with Improvement in WHO Functional Class		24 weeks
Phase 3: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score	REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk	24 weeks
Phase 3: Change from Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire Score	PAH-SYMPACT is a patient reported outcome instrument developed to assess PAH symptoms and impacts	24 weeks
Phase 2b: Time to Clinical Worsening		24 weeks

Collaborators and Investigators

• Sponsor: Aerovate Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Actual): August 9, 2024
• Study Completion (Actual): August 9, 2024

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; Pulmonary; PAH; Lungs; AV-101; imatinib; IMPAHCT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: AV-101-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes