American journal of respiratory and critical care medicine · 2026
Phase 2b trial of inhaled imatinib for treatment of pulmonary arterial hypertension.
СтатьяКлиническое исследование II фазыРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Hill Nicholas S, Gillies Hunter, Chakinala Murali M, Feldman Jeremy P, Hoeper Marius M, Jing Zhi-Cheng, Mclaughlin Vallerie V, Rosenkranz Stephan, Escribano-Subias Pilar, Ghio Stefano, Gomberg-Maitland Mardi, Habib Naomi, Kopec Grzegorz, Langleben David, Lescano Adrian, Ramirez Alicia, Rischard Franz, Sitbon Olivier, Skride Andris, Dake Ben T, Khindri Sanjeev, Langley Jonathan, Niven Ralph, Zhang Xiaosha, Humbert Marc
Аннотация
INTRODUCTION/BACKGROUND: Oral imatinib, a tyrosine kinase inhibitor, demonstrated efficacy in pulmonary arterial hypertension (PAH) studies but was poorly tolerated. We report here the findings of a study using a dry powder inhaled version of imatinib (AV-101).
AIMS AND OBJECTIVES: IMPAHCT (NCT05036135) was designed to assess the efficacy, safety, tolerability, and optimal dose of AV-101 as an add-on treatment for PAH, using a novel phase 2b/3 adaptive study design. Here we report the phase 2b results.
METHODS: The phase 2b part assessed 3 doses of AV-101 (10 mg, 35 mg, and 70 mg), administered twice a day, vs placebo for 24 weeks as an add-on treatment in adults with PAH. Change in pulmonary vascular resistance (PVR) was the primary endpoint. Secondary endpoints included the change in other hemodynamic variables, 6-minute walk distance (6MWD), World Health Organization functional class, Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score, clinical worsening, clinical improvement, N-terminal proB-type natriuretic peptide, quality of life, safety, and tolerability.
RESULTS: In total, 202 patients were randomized. Baseline characteristics were broadly well balanced between groups. There were no significant improvements vs placebo in PVR (42.8 dyn·s·cm-5 in the AV-101 10-mg group, -5.5 dyn·s·cm-5 in the AV-101 35-mg group, -57.0 dyn·s·cm-5 in the AV-101 70-mg group, and 19.5 dyn·s·cm-5 in the placebo group), 6MWD, or other secondary endpoints at any dose. Pharmacokinetic measures supported delivery of drug to the lung and into the plasma. The incidence of cough increased with dose. No safety concerns were identified.
CONCLUSIONS: Add-on dry powder inhaled imatinib (AV-101) was not effective in lowering PVR at any of the studied doses in patients with PAH. The phase 3 part of the IMPAHCT study was halted.
AIMS AND OBJECTIVES: IMPAHCT (NCT05036135) was designed to assess the efficacy, safety, tolerability, and optimal dose of AV-101 as an add-on treatment for PAH, using a novel phase 2b/3 adaptive study design. Here we report the phase 2b results.
METHODS: The phase 2b part assessed 3 doses of AV-101 (10 mg, 35 mg, and 70 mg), administered twice a day, vs placebo for 24 weeks as an add-on treatment in adults with PAH. Change in pulmonary vascular resistance (PVR) was the primary endpoint. Secondary endpoints included the change in other hemodynamic variables, 6-minute walk distance (6MWD), World Health Organization functional class, Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score, clinical worsening, clinical improvement, N-terminal proB-type natriuretic peptide, quality of life, safety, and tolerability.
RESULTS: In total, 202 patients were randomized. Baseline characteristics were broadly well balanced between groups. There were no significant improvements vs placebo in PVR (42.8 dyn·s·cm-5 in the AV-101 10-mg group, -5.5 dyn·s·cm-5 in the AV-101 35-mg group, -57.0 dyn·s·cm-5 in the AV-101 70-mg group, and 19.5 dyn·s·cm-5 in the placebo group), 6MWD, or other secondary endpoints at any dose. Pharmacokinetic measures supported delivery of drug to the lung and into the plasma. The incidence of cough increased with dose. No safety concerns were identified.
CONCLUSIONS: Add-on dry powder inhaled imatinib (AV-101) was not effective in lowering PVR at any of the studied doses in patients with PAH. The phase 3 part of the IMPAHCT study was halted.