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

NCT05036135 | Terminated Phase 2 FDA Drug

• 1 other identifier: AV-101-002
• Study Type: interventional
• Target: 202
• Locations: 25 countries
• Sites: 119

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; Lungs; Pulmonary; PAH; AV-101; imatinib; IMPAHCT

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• 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: Time to Clinical Worsening

  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

  24 weeks

Study Arms (4)

AV-101 10 mg

EXPERIMENTAL

Drug: AV-101

AV-101 35 mg

EXPERIMENTAL

Drug: AV-101

AV-101 70 mg

EXPERIMENTAL

Drug: AV-101

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AV-101 DRUG

AV-101 (imatinib) administered via dry powder inhalation

AV-101 10 mg; AV-101 35 mg; AV-101 70 mg

Placebo DRUG

Placebo administered via dry powder inhalation

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PAH belonging to one of the subgroups:
• I/HPAH, PAH-CTD,
• 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),
• HIV associated or
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Aerovate Therapeutics: lead

Study Sites (128)

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, 85012, United States

Location

University of Arizona, Department of Medicine

Tucson, Arizona, 85724, United States

Location

UCLA/David Geffen School of Medicine-Pulmonary and Criticial Care

Los Angeles, California, 90024, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Cedars-Sinai Medical Center, Pulmonary & Critical Care

Los Angeles, California, 90048, United States

Location

Dept of Veterans Affairs Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California

San Francisco, California, 94143, United States

Location

LA Biomedical Research Institute Harbor

Torrance, California, 90509, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

George Washington University Medical Faculty Associates, Inc.

Washington D.C., District of Columbia, 20073, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Orlando Heart Center

Orlando, Florida, 32804, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tufts Medical Center, Inc.

Boston, Massachusetts, 02111, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center- Hematology/Oncology Section

Omaha, Nebraska, 68198, United States

Location

The Unviersity of New Mexico - UNM Hospitals

Albuquerque, New Mexico, 87131, United States

Location

New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

NYU Langone Seaport

New York, New York, 10016, United States

Location

Duke University Medical Center - Duke South Clinic

Durham, North Carolina, 27710, United States

Location

The Lindner Center for Research and Education

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Bend Memorial Clinic

Oregon City, Oregon, 97701, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Stat Care Pulmonary Consultants, PLLC

Knoxville, Tennessee, 37919, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Sentara Medical Group - Sentara Pulmonary & Critical Care Specialists

Norfolk, Virginia, 23507, United States

Location

Hospital Britanico de Buenos Aires

Buenos Aires, 1134, Argentina

Location

Nexo Salud Investigación Clínica

Buenos Aires, 1425, Argentina

Location

Sanatorio de la Trinidad Mitre

Buenos Aires, C1039AAO, Argentina

Location

Cardiología Palermo

CABA, 1425, Argentina

Location

Insituto Medico DAMIC

Córdoba, 5009, Argentina

Location

Hospital Italiano de Cordoba

Córdoba, X5004FJE, Argentina

Location

Hospital Dr. Jose Maria Cullen

Santa Fe, S300EOZ, Argentina

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Concord Repatriation General Hospital

Concord West, New South Wales, 2138, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Fiona Stanley Hospital

Murdoch, 6150, Australia

Location

AKH - Medizinische Universitat Wien

Vienna, 1090, Austria

Location

Hopital Erasme - Cliniques Universitaires de Bruxelles

Brussels, 1070, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90035-074, Brazil

Location

Heart Institute - University of Sao Paulo

São Paulo, 05403, Brazil

Location

The Governors of the University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

London Health Science Centre

London, Ontario, N6A 5W9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Centro de Investigaciones Clinicas de la Universidad Catolica

Santiago, 8330024, Chile

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Chongqing Medical University - The First Affiliated Hospital

Chongqing, 40016, China

Location

Guangdong Provincial People's Hospital

Guangdong, 510000, China

Location

Central South University - The Second Xiangya Hospital

Hunan, 410011, China

Location

Yanan Hospital of Kunming City

Kunming, 650051, China

Location

Gansu Provincial People's Hospital

Lanzhou, 730000, China

Location

Southeast University (SEU) - Zhongda Hospital

Nanjing, 210009, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200437, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

Groupement Hospitalier Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, Cedex, 94275, France

Location

Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel

Bron, 69677, France

Location

Hôpital Nord - CHU Marseille

Marseille, 94275, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 1307, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen

Giesen, 35292, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

München Klinik Bogenhausen

München, 81925, Germany

Location

University General Hospital Attikon

Athens, 10676, Greece

Location

Cardiosurgery Hospital

Kallithea, 17674, Greece

Location

AHEPA General Hospital of Thessaloniki

Thessaloniki, 54637, Greece

Location

The Lady Davis Carmel Medical Center

Haifa, 34362, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 91999, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti - Foggia

Foggia, 71122, Italy

Location

Ospedale San Giuseppe - Fatebenefratelli

Milan, 20123, Italy

Location

Azienda Socio Sanitaria Territoriale di Monza

Monza, 20900, Italy

Location

Azienda Ospedaliera Vincenzo Monaldi

Napoli, 80131, Italy

Location

Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione

Palermo, 90127, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I

Rome, 137, Italy

Location

Pauls Stradins Clinical University Hospital

Riga, 1002, Latvia

Location

CICUM San Miguel

Guadalajara, Jalisco, 44160, Mexico

Location

Unidad de Investigacion Clinica en Medicina S.C.

Monterrey, Nuevo León, 64718, Mexico

Location

Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera

Mexico City, 14080, Mexico

Location

Universidad Autonoma de Nuevo Leon, Hospital Universitario

Monterrey, 64460, Mexico

Location

Amsterdam UMC, Locatie VUMC

Amsterdam, 1081 HV, Netherlands

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, 31-202, Poland

Location

Bieganski Provincial Specialist Hospital

Lodz, 91-347, Poland

Location

Szpital Kliniczny Przemienienia Pańskiego UM im. Marcinkowskiego

Poznan, 61-848, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego

Wroclaw, 50-556, Poland

Location

Hospital Garcia de Orta, EPE

Almada, 2805-267, Portugal

Location

Hospital Pulido Valente

Lisbon, 1649-035, Portugal

Location

CHUPorto

Porto, 4099-001, Portugal

Location

Cardiopulmonary Research Center

Guaynabo, 00968, Puerto Rico

Location

National University Hospital

Singapore, 119074, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Center of Chest Disease Johannesburg

Johannesburg, 2193, South Africa

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hosp. Universitario Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital 12 de Octubre

Madrid, 28014, Spain

Location

Universidad Autonoma de Madrid

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29071, Spain

Location

Hospital universtario de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Universitario Marques de Valdecilla

Santander, 39003, Spain

Location

Hospital Universitario de Toledo

Toledo, 45007, Spain

Location

Norrlands Universitetssjukhus

Umeå, 907 37, Sweden

Location

Imperial College Healthcare NHS Trust

London, England, W12 0HS, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, NE7 7DN, United Kingdom

Location

Related Publications (2)

• Gillies H, Chakinala MM, Dake BT, Feldman JP, Hoeper MM, Humbert M, Jing ZC, Langley J, McLaughlin VV, Niven RW, Rosenkranz S, Zhang X, Hill NS. IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension. Pulm Circ. 2024 Mar 25;14(1):e12352. doi: 10.1002/pul2.12352. eCollection 2024 Jan.

  PMID: 38532768 DERIVED

• Gillies H, Niven R, Dake BT, Chakinala MM, Feldman JP, Hill NS, Hoeper MM, Humbert M, McLaughlin VV, Kankam M. AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study. ERJ Open Res. 2023 Mar 13;9(2):00433-2022. doi: 10.1183/23120541.00433-2022. eCollection 2023 Mar.

  PMID: 36923571 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: September 5, 2021
• Study Start: December 2, 2021
• Primary Completion: August 9, 2024
• Study Completion: August 9, 2024
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3); PR (1); SE (1); PL (4); ES (9); CA (4); BR (2); AU (1); CN (9); SG (2); GB (4); AR (7); DE (4); US (39); ZA (1); BE (2); GR (3); IL (3); FR (5); IT (7); LA (1); ME (4); NL (1); CL (1); CZ (1)