Phase 2b trial of inhaled imatinib for treatment of pulmonary arterial hypertension.

We report here the findings of a study using a dry powder inhaled version of imatinib (AV-101).

我们报告了一项使用伊马替尼干粉吸入剂（AV-101）的研究结果。

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.

IMPAHCT (NCT05036135)旨在通过一种新颖的2b/3期自适应研究设计，评估AV-101作为PAH附加治疗的疗效、安全性、耐受性和最佳剂量。

Here we report the phase 2b results.

在这里我们报告了2b期的结果。

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.

第2b阶段评估了三种剂量的AV-101（10毫克、35毫克和70毫克），每天两次，与安慰剂相比，为期24周作为成人PAH的附加治疗。

Change in pulmonary vascular resistance (PVR) was the primary endpoint.

肺血管阻力（PVR）的变化是主要终点。

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.

次要终点包括其他血流动力学变量的变化、6分钟步行距离（6MWD）、世界卫生组织功能分级、肺动脉高压疾病管理轻量版2风险评分、临床恶化、临床改善、N末端前体B型利钠肽、生活质量、安全性和耐受性。

Results

In total, 202 patients were randomized.

总共，202名患者被随机分配。

Baseline characteristics were broadly well balanced between groups.

各组之间的基线特征大致平衡。

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.

与安慰剂相比，AV-101 10mg组的PVR为42.8 dyn·s·cm-5，AV-101 35mg组为-5.5 dyn·s·cm-5，AV-101 70mg组为-57.0 dyn·s·cm-5，而安慰剂组为19.5 dyn·s·cm-5，各剂量组在PVR、6分钟步行距离（6MWD）或其他次要终点上均未显示出显著改善。

Pharmacokinetic measures supported delivery of drug to the lung and into the plasma.

药代动力学测量支持药物被输送到肺部并进入血浆。

The incidenceof cough increased with dose.

咳嗽的发生率随着剂量的增加而增加。

No safety concerns were identified.

未发现任何安全问题。

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.

在研究的任何剂量下，附加干粉吸入伊马替尼（AV-101）对降低肺动脉高压（PAH）患者的肺血管阻力（PVR）均无效。

The phase 3 part of the IMPAHCT study was halted.

IMPAHCT研究的第三阶段部分已被停止。