IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension

25 March 2024

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 

https://doi.org/10.1002/pul2.12352

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.

Read the full research article


 

Share:

Other materials on this topic

13 November 2024

Reply to the letter to the editor entitled “Bridging the species divide: The limits of rat models in capturing human PVOD mechanisms” by Perros F. et al.

Dear Editor,
We thank Drs. Perros, Chaveroux, and Montani for their interest in our articles describing the activation of the integrated stress response (ISR) pathway as a mechanism underlying the pathogenesis of pulmonary veno-occlusive disease (PVOD), based on the rat mitomycin C (MMC) model of PVOD.

Pulmonary Circulation
18 October 2024

Congruency between clinician-assessed risk and calculated risk of 1-year mortality in patients with pulmonary arterial hypertension: A retrospective chart review

The objective of this analysis was to compare clinician-based and formally calculated risk assessments by REVEAL Lite 2 and COMPERA 2.0 and to characterize parenteral prostacyclin utilization within 90 days of baseline in high-risk patients. A multisite, double-blind, retrospective chart review of patients with pulmonary arterial hypertension (PAH) was conducted with an index period of January 2014–March 2017.

Pulmonary Circulation
Additional comments are available to members. Login or register to become a member today
RegisterorLogin to view

More from Pulmonary Circulation

Show more details

A collection of up-to-date abstracts from our premier, international, peer-reviewed, medical research journal dedicated exclusively to pulmonary circulation and pulmonary vascular disease. 

High gestational leucine level dampens WDPCP/MAPK signaling to impair the EMT and migration of cardiac microvascular endothelial cells in congenital heart defects
Pulmonary hypertension during high-dose GM-CSF therapy of autoimmune pulmonary alveolar proteinosis
Asymmetric right ventricular myocardial work correlates with gold standard measurements of cardiac function in pulmonary hypertension
Effects of dopamine β-hydroxylase inhibition in pressure overload-induced right ventricular failure
The metabolic and physiologic impairments underlying long COVID associated exercise intolerance
3-year quality of life, functional performance, and long-term survival after acute pulmonary embolism; A prospective study
Reply to the letter to the editor entitled “Bridging the species divide: The limits of rat models in capturing human PVOD mechanisms” by Perros F. et al.
Bridging the species divide: The limits of rat models in capturing human PVOD mechanisms
Infection and pulmonary vascular diseases consortium: United against a global health challenge
Delta-like ligand 4 inhibitor drug treatment induces pulmonary hypertension in cancer clinical trials
Quantitative pulmonary perfusion in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension
Comorbidity profiles and pulmonary embolism risk assessment: Leveraging the Charlson Comorbidity Index for improved prognostication in a national data set
Hemodynamic markers independent of pulmonary capillary wedge pressure can discriminate between pre and postcapillary exercise-induced pulmonary hypertension
Extracorporeal membrane oxygenation (ECMO) support for children with pulmonary hypertension: A single-institutional experience of outcomes
Transcriptome analyses reveal common immune system dysregulation in PAH patients and Kcnk3-deficient rats