IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension
Abstract AV‐101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. Inh...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Pulmonary Circulation |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/pul2.12352 |
| _version_ | 1797236724181499904 |
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| author | Hunter Gillies Murali M. Chakinala Benjamin T. Dake Jeremy P. Feldman Marius M. Hoeper Marc Humbert Zhi‐Cheng Jing Jonathan Langley Vallerie V. McLaughlin Ralph W. Niven Stephan Rosenkranz Xiaosha Zhang Nicholas S. Hill |
| author_facet | Hunter Gillies Murali M. Chakinala Benjamin T. Dake Jeremy P. Feldman Marius M. Hoeper Marc Humbert Zhi‐Cheng Jing Jonathan Langley Vallerie V. McLaughlin Ralph W. Niven Stephan Rosenkranz Xiaosha Zhang Nicholas S. Hill |
| author_sort | Hunter Gillies |
| collection | DOAJ |
| description | Abstract AV‐101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double‐blind, placebo‐controlled, dose‐ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV‐101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6‐min walk distance), safety, and tolerability of AV‐101 dose levels in subjects with pulmonary arterial hypertension using background therapies. The study has an operationally seamless, adaptive design allowing for continuous recruitment. It includes three parts; subjects enrolled in Part 1 (phase 2b dose–response portion) or Part 2 (phase 3 intermediate portion) will be randomized 1:1:1:1 to 10, 35, 70 mg AV‐101, or placebo (twice daily), respectively. Subjects enrolled in Part 3 (phase 3 optimal dose portion) will be randomized 1:1 to the optimal dose of AV‐101 and placebo (twice daily), respectively. All study parts include a screening period, a 24‐week treatment period, and a 30‐day safety follow‐up period; the total duration is ∼32 weeks. Participation is possible in only one study part. IMPAHCT has the potential to advance therapies for patients with pulmonary arterial hypertension by assessing the efficacy and safety of a novel investigational drug‐device combination (AV‐101) using an improved study design that has the potential to save 6‐12 months of development time. ClinicalTrials.gov Identifier: NCT05036135. |
| first_indexed | 2024-04-24T17:08:24Z |
| format | Article |
| id | doaj.art-6cca6181d66a4a5aadc281acfa6b68ed |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-24T17:08:24Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-6cca6181d66a4a5aadc281acfa6b68ed2024-03-28T19:28:30ZengWileyPulmonary Circulation2045-89402024-01-01141n/an/a10.1002/pul2.12352IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertensionHunter Gillies0Murali M. Chakinala1Benjamin T. Dake2Jeremy P. Feldman3Marius M. Hoeper4Marc Humbert5Zhi‐Cheng Jing6Jonathan Langley7Vallerie V. McLaughlin8Ralph W. Niven9Stephan Rosenkranz10Xiaosha Zhang11Nicholas S. Hill12Aerovate Therapeutics Waltham Massachusetts USADivision of Pulmonary and Critical Care Medicine Washington University in St. Louis St. Louis MissourI USAAerovate Therapeutics Waltham Massachusetts USASummit Health/BMC Bend Oregon USADepartment of Respiratory Medicine and Infectious Diseases Hannover Medical School Hannover GermanyService de Pneumologieet Soins Intensifs Respiratoires, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre Université Paris–Saclay, INSERMUMR_S 999 Le Kremlin‐Bicêtre FranceDepartment of Cardiology, Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences Southern Medical University Guangzhou ChinaAerovate Therapeutics Waltham Massachusetts USACardiology Clinic, Frankel Cardiovascular Center University of Michigan Ann Arbor Michigan USAAerovate Therapeutics Waltham Massachusetts USADepartment of Internal Medicine III, Cologne Cardiovascular Research Center, Heart Center Universityof Cologne Cologne GermanyAerovate Therapeutics Waltham Massachusetts USAPulmonary Critical Care and Sleep Division Tufts Medical Center Boston Massachusetts USAAbstract AV‐101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double‐blind, placebo‐controlled, dose‐ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV‐101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6‐min walk distance), safety, and tolerability of AV‐101 dose levels in subjects with pulmonary arterial hypertension using background therapies. The study has an operationally seamless, adaptive design allowing for continuous recruitment. It includes three parts; subjects enrolled in Part 1 (phase 2b dose–response portion) or Part 2 (phase 3 intermediate portion) will be randomized 1:1:1:1 to 10, 35, 70 mg AV‐101, or placebo (twice daily), respectively. Subjects enrolled in Part 3 (phase 3 optimal dose portion) will be randomized 1:1 to the optimal dose of AV‐101 and placebo (twice daily), respectively. All study parts include a screening period, a 24‐week treatment period, and a 30‐day safety follow‐up period; the total duration is ∼32 weeks. Participation is possible in only one study part. IMPAHCT has the potential to advance therapies for patients with pulmonary arterial hypertension by assessing the efficacy and safety of a novel investigational drug‐device combination (AV‐101) using an improved study design that has the potential to save 6‐12 months of development time. ClinicalTrials.gov Identifier: NCT05036135.https://doi.org/10.1002/pul2.12352dry powder inhalereffectivenessstudy designtolerabilitytyrosine kinase inhibitor |
| spellingShingle | Hunter Gillies Murali M. Chakinala Benjamin T. Dake Jeremy P. Feldman Marius M. Hoeper Marc Humbert Zhi‐Cheng Jing Jonathan Langley Vallerie V. McLaughlin Ralph W. Niven Stephan Rosenkranz Xiaosha Zhang Nicholas S. Hill IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension Pulmonary Circulation dry powder inhaler effectiveness study design tolerability tyrosine kinase inhibitor |
| title | IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension |
| title_full | IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension |
| title_fullStr | IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension |
| title_full_unstemmed | IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension |
| title_short | IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension |
| title_sort | impahct a randomized phase 2b 3 study of inhaled imatinib for pulmonary arterial hypertension |
| topic | dry powder inhaler effectiveness study design tolerability tyrosine kinase inhibitor |
| url | https://doi.org/10.1002/pul2.12352 |
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