Gillies Hunter, Chakinala Murali M, Dake Benjamin T, Feldman Jeremy P, Hoeper Marius M, Humbert Marc, Jing Zhi-Cheng, Langley Jonathan, McLaughlin Vallerie V, Niven Ralph W, Rosenkranz Stephan, Zhang Xiaosha, Hill Nicholas S
Aerovate Therapeutics Waltham Massachusetts USA.
Division of Pulmonary and Critical Care Medicine Washington University in St. Louis St. Louis MissourI USA.
Pulm Circ. 2024 Mar 25;14(1):e12352. doi: 10.1002/pul2.12352. eCollection 2024 Jan.
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. nhaled Iatinib ulmonary rterial ypertension linical rial (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.
AV-101（伊马替尼）吸入粉，一种旨在针对肺动脉高压潜在病理生物学的伊马替尼吸入干粉制剂，在一项1期单剂量和多剂量递增研究中，健康成年人对其耐受性普遍良好。吸入伊马替尼治疗肺动脉高压临床试验（IMPAHCT；NCT05036135）是一项2b/3期、随机、双盲、安慰剂对照、剂量范围和确证性研究。IMPAHCT旨在确定最佳AV-101剂量（2b期主要终点：肺血管阻力），并评估使用背景疗法的肺动脉高压患者中AV-101剂量水平的疗效（3期主要终点：6分钟步行距离）、安全性和耐受性。该研究采用操作无缝的适应性设计，允许持续招募。它包括三个部分；参加第1部分（2b期剂量反应部分）或第2部分（3期中间部分）的受试者将分别按1:1:1:1随机分配至10、35、70毫克AV-101或安慰剂（每日两次）。参加第3部分（3期最佳剂量部分）的受试者将分别按1:1随机分配至AV-101最佳剂量和安慰剂（每日两次）。所有研究部分均包括筛选期、24周治疗期和30天安全性随访期；总时长约为32周。仅可参与一个研究部分。IMPAHCT有可能通过使用一种有可能节省6至12个月研发时间的改进研究设计，评估一种新型研究性药物-器械组合（AV-101）的疗效和安全性，从而推进肺动脉高压患者的治疗。ClinicalTrials.gov标识符：NCT05036135。
