Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial - Follow Up Long Term Extension (IMPAHCT-FUL) (IMPAHCT-FUL)

A Long-Term Extension, Multi-Center Safety Study of AV-101 in Subjects With Pulmonary Arterial Hypertension (PAH) Who Have Completed Study AV-101-002 (IMPAHCT-FUL)

IMPAHCT-FUL: Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial - Follow Up Long Term Extension (LTE) Trial was a follow up study to establish the long-term safety of AV-101. Subjects who successfully completed the 24-week placebo-controlled parent trial (AV-101-002, NCT#05036135) were offered the opportunity to continue into this LTE study. Subjects who enrolled in the study were to receive one of three active AV-101 doses until such time as the optimal dose was selected in the parent study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Sanatorio de la Trinidad Mitre
  • Buenos Aires, Argentina, 1425
    • Nexo Salud Investigacion Clinica
  • Buenos Aires, Argentina, 1425
    • Cardiologia Palmero
  • Córdoba, Argentina, 5009
    • Insituto Medico DAMIC
  • Santa Fe, Argentina, S3000EOZ
    • Hospital Dr. Jose Maria Cullen
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred 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
• Belgium
  • Bruxelles, Belgium, 1070
    • Cliniques universitaires de Bruxelles Hopital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • 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
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
• Colombia
  • Floridablanca, Colombia, 20-97
    • Instituto Neumologico del Oriente S.A.
• France
  • Le Kremlin-Bicêtre, France, 94275
    • Groupement Hospitalier Sud - Hôpital Bicêtre
  • Montpellier, France, 34295
    • Hopital Arnaud de Villeneuve
  • Strasbourg, France, 67091
    • Les Hôpitaux Universitaires de Strasbourg
• Germany
  • Dresden, Germany, 1307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Gießen, Germany, 35392
    • Universitaetsklinikum Giessen Und Marburg Gmbh Standort Giessen
  • Heidelberg, Germany, 69126
    • Universitaetsklinikum Heidelberg
• Israel
  • Jerusalem, Israel, 91999
    • Hadassah University Hospital - Ein Kerem
• Italy
  • Foggia, Italy, 71122
    • Azienda Ospedaliero Universitaria Ospedali Riuniti - Foggia
  • Milan, Italy, 20123
    • Ospedale San Giuseppe - Fatebenefratelli
  • Monza, Italy, 20900
    • Fondazione IRCCS San Gerardo dei Tintori
  • 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
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • CICUM San Miguel
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Unidad de Investigacion Clinica en Medicina S.C.
• Poland
  • Kraków, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Poznań, Poland, 61-848
    • Szpital Kliniczny Przemienienia Pańskiego UM im. Marcinkowskiego
  • Łódź, Poland, 91-347
    • Wojewódzki Specjalistyczny Szpital im. Dr. Wł. Biegańskiego w Łodzi
• Portugal
  • Almada, Portugal, 2805-267
    • Hospital Garcia de Orta, EPE
  • Lisboa, Portugal, 1769-001
    • Hospital Pulido Valente
• 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
  • Las Palmas De Gran Canaria, Spain, 35010
    • Hosp. Universitario Gran Canaria Doctor Negrin
  • Madrid, Spain, 28014
    • Hospital 12 de Octubre
  • 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
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialist. 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, 90024
      • UCLA/David Geffen School of Medicine-Pulmonary and Criticial Care
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GW Medical Faculty Associates
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center, Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

To be eligible, a participant is required to be or have:

• Consented to participate in the LTE and has successfully completed the placebo-controlled 24-week Study AV-101-002.

Key Exclusion Criteria:

Subjects meeting any of the following criteria:

• The Investigator believes that it would not be in the best interest of the subject to be included in the LTE e.g., for clinical or social reasons.
• Subjects who were not compliant with study medication in AV-101-002 as assessed by the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo Crossover AV-101 10 mg; Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 10 milligrams (mg) administered twice daily (BID) via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: Placebo Crossover AV-101 35 mg; Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 35 mg administered BID via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: Placebo Crossover AV-101 70 mg; Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 70 mg administered BID via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: Continuing AV-101 10 mg; Participants who previously received AV-101 10 mg in AV-101-002 received AV-101 (imatinib) 10 mg administered BID via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: Continuing AV-101 35 mg; Participants who previously received AV-101 35 mg in AV-101-002 received AV-101 (imatinib) 35 mg administered BID via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation
Experimental: Continuing AV-101 70 mg; Participants who previously received AV-101 70 mg in AV-101-002 received AV-101 (imatinib) 70 mg administered BID via dry powder inhalation.	Drug: AV-101; AV-101 (imatinib) administered via dry powder inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	From date of first dose to 30 days after date of last dose (up to approximately 21 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the 6MWD		Baseline, weeks 4,12 and 24, and every 12 weeks up to study completion
Change from baseline in NT-proBNP		Baseline, weeks 4,12 and 24, and every 12 weeks up to study completion
Change from baseline in Right Ventricular (RV) function (e.g. TAPSE, RVFAC, RV/PA coupling, TRJV etc.) as measured by Resting Transthoracic Echocardiography		Baseline, week 24, and every 12 weeks up to study completion
Time to Clinical Worsening	Clinical Worsening Events will be defined as: Death (all causes); Hospitalization for worsening PAH; Initiation of parenteral prostanoids (subcutaneous or intravenous infusion); ≥ 15% decline from baseline in 6MWD accompanied with continued or worsening to WHO FC III or IV symptoms. The decline in 6MWD must be confirmed with a repeat test on a different day within 2 weeks Time to clinical worsening is the number of days between the earliest occurrence of the clinical worsening component and the date of the first dose in the parent trial.	Through Study completion, anticipated to be approximately 3 years

Collaborators and Investigators

• Sponsor: Aerovate Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Actual): August 8, 2024
• Study Completion (Actual): August 8, 2024

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; Pulmonary; PAH; Lungs; AV-101; imatinib; IMPAHCT; IMPAHCT-FUL
• 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-101-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No