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

Pulmonary Arterial Hypertension Clinical Trial

— IMPAHCT  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05036135
• Other study ID #: AV-101-002
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 2, 2021
• Est. completion date: January 2025

Study information

• Verified date: June 2024
• Source: Aerovate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 462
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• AV-101
AV-101 (imatinib) administered via dry powder inhalation
• Placebo
Placebo administered via dry powder inhalation

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Aerovate Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Latvia,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Singapore,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2b: Change from Baseline in Pulmonary Vascular Resistance (PVR)		24 weeks
Primary	Phase 3: Change from Baseline in Six Minute Walk Distance (6MWD)		24 weeks
Secondary	Phase 2b: Change from Baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP)		24 weeks
Secondary	Phase 2b: Change from Baseline in Six Minute Walk Distance (6MWD)		24 weeks
Secondary	Phase 2b: Time to Clinical Worsening		24 weeks
Secondary	Phase 2b: Proportion of Subjects with Improvement in WHO Functional Class		24 weeks
Secondary	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
Secondary	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
Secondary	Phase 3: Change from Baseline in NT-proBNP		24 weeks
Secondary	Phase 3: Time to Clinical Worsening		24 weeks
Secondary	Phase 3: Proportion of Subjects with Improvement in WHO Functional Class		24 weeks
Secondary	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
Secondary	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