Clinical trial NCT05036135: A Study of AV-101 (Dry Powder Inhaled Imatinib) in Patients With Pulmonary Arterial Hypertension (PAH)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension
Lungs
Pulmonary
PAH
AV-101
imatinib
IMPAHCT
Lead sponsor: Aerovate Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-09-05
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 2b: Change from Baseline in Pulmonary Vascular Resistance (PVR)
timeFrame: 24 weeks
measure: Phase 3: Change from Baseline in Six Minute Walk Distance (6MWD)
timeFrame: 24 weeks
Secondary outcomes:
measure: Phase 2b: Change from Baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP)
timeFrame: 24 weeks
measure: Phase 2b: Change from Baseline in Six Minute Walk Distance (6MWD)
timeFrame: 24 weeks
measure: Phase 2b: Time to Clinical Worsening
timeFrame: 24 weeks
measure: Phase 2b: Proportion of Subjects with Improvement in WHO Functional Class
timeFrame: 24 weeks
measure: Phase 2b: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score
timeFrame: 24 weeks
measure: Phase 2b: Change from Baseline in Health-Related Quality of Life emPHasis-10 Questionnaire Score
timeFrame: 24 weeks
measure: Phase 3: Change from Baseline in NT-proBNP
timeFrame: 24 weeks
measure: Phase 3: Time to Clinical Worsening
timeFrame: 24 weeks
measure: Phase 3: Proportion of Subjects with Improvement in WHO Functional Class
timeFrame: 24 weeks
measure: Phase 3: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score
timeFrame: 24 weeks
measure: Phase 3: Change from Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire Score
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Department of Medicine
state: Arizona
city: Los Angeles
country: United States
facility: UCLA/David Geffen School of Medicine-Pulmonary and Criticial Care
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Pulmonary & Critical Care
state: California
city: Los Angeles
country: United States
facility: Dept of Veterans Affairs Greater Los Angeles Healthcare System
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Torrance
country: United States
facility: LA Biomedical Research Institute Harbor
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates, Inc.
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Heart Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Tufts Medical Center, Inc.
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: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center- Hematology/Oncology Section
state: Nebraska
city: Albuquerque
country: United States
facility: The Unviersity of New Mexico - UNM Hospitals
state: New Mexico
city: Brooklyn
country: United States
facility: New York-Presbyterian Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Seaport
state: New York
city: Durham
country: United States
facility: Duke University Medical Center - Duke South Clinic
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research and Education
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oregon City
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: Stat Care Pulmonary Consultants, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Medical Group - Sentara Pulmonary & Critical Care Specialists
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Nexo Salud Investigación Clínica
city: Buenos Aires
country: Argentina
facility: Sanatorio de la Trinidad Mitre
city: Caba
country: Argentina
facility: Cardiología Palermo
city: Córdoba
country: Argentina
facility: Insituto Medico DAMIC
city: Córdoba
country: Argentina
facility: Hospital Italiano de Cordoba
city: Santa Fe
country: Argentina
facility: Hospital Dr. Jose Maria Cullen
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord West
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Vienna
country: Austria
facility: AKH - Medizinische Universitat Wien
city: Brussels
country: Belgium
facility: Hopital Erasme - Cliniques Universitaires de Bruxelles
city: Leuven
country: Belgium
facility: UZ Leuven
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
city: São Paulo
country: Brazil
facility: Heart Institute - University of Sao Paulo
city: Calgary
country: Canada
facility: The Governors of the University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Santiago
country: Chile
facility: Centro de Investigaciones Clinicas de la Universidad Catolica
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Chongqing
country: China
facility: Chongqing Medical University - The First Affiliated Hospital
city: Guangdong
country: China
facility: Guangdong Provincial People's Hospital
city: Hunan
country: China
facility: Central South University - The Second Xiangya Hospital
city: Kunming
country: China
facility: Yanan Hospital of Kunming City
city: Lanzhou
country: China
facility: Gansu Provincial People's Hospital
city: Nanjing
country: China
facility: Southeast University (SEU) - Zhongda Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Le Kremlin-Bicêtre
country: France
facility: Groupement Hospitalier Sud - Hôpital Bicêtre
state: Cedex
city: Bron
country: France
facility: Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve
city: Strasbourg
country: France
facility: Les Hôpitaux Universitaires de Strasbourg
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Giesen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: München
country: Germany
facility: München Klinik Bogenhausen
city: Athens
country: Greece
facility: University General Hospital Attikon
city: Kallithéa
country: Greece
facility: Cardiosurgery Hospital
city: Thessaloníki
country: Greece
facility: AHEPA General Hospital of Thessaloniki
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Foggia
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti - Foggia
city: Milan
country: Italy
facility: Ospedale San Giuseppe - Fatebenefratelli
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza
city: Napoli
country: Italy
facility: Azienda Ospedaliera Vincenzo Monaldi
city: Palermo
country: Italy
facility: Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Guadalajara
country: Mexico
facility: CICUM San Miguel
state: Jalisco
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina S.C.
state: Nuevo León
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera
city: Monterrey
country: Mexico
facility: Universidad Autonoma de Nuevo Leon, Hospital Universitario
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie VUMC
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Pańskiego UM im. Marcinkowskiego
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
city: Łódź
country: Poland
facility: Bieganski Provincial Specialist Hospital
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, EPE
city: Lisboa
country: Portugal
facility: Hospital Pulido Valente
city: Porto
country: Portugal
facility: CHUPorto
city: Guaynabo
country: Puerto Rico
facility: Cardiopulmonary Research Center
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Johannesburg
country: South Africa
facility: Center of Chest Disease Johannesburg
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Hosp. Universitario Gran Canaria Doctor Negrin
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Universidad Autonoma de Madrid
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital universtario de Salamanca
city: Santander
country: Spain
facility: Hosp. Universitario Marques de Valdecilla
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: England
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Newcastle
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
References: