Pamufetinib (TAS-115) for chronic fibrosing interstitial lung diseases with a progressive phenotype: a double-blind, multicenter, phase 2b clinical trial.

Pamufetinib (also known as TAS-115) is a novel oral antifibrotic tyrosine kinase inhibitor in development for CF-ILD with a progressive phenotype.

Pamufetinib（也被称为TAS-115）是一种正在开发中的新型口服抗纤维化酪氨酸激酶抑制剂，用于治疗具有进展表型的CF-ILD。

Background

We sought to evaluate the dose-response of pamufetinib monotherapy in patients with CF-ILD including idiopathic pulmonary fibrosis (IPF) with a progressive phenotype despite an antifibrotic treatment.

我们旨在评估帕穆非替尼单药治疗在患有慢性纤维化间质性肺病（包括尽管接受抗纤维化治疗仍表现为进行性表型的特发性肺纤维化（IPF））患者中的剂量-反应关系。

Methods

In this double-blind, multicenter, active-controlled phase 2b study, patients with CF-ILD with a progressive phenotype (defined as ≥ 5% decline in the annual percent predicted FVC [%FVC] despite treatment with nintedanib or pirfenidone and an %FVC ≥ 50%) were randomized 1:1:1 to pamufetinib 50 mg, 100 mg, or control (nintedanib or pirfenidone) for ≥ 6 weeks.

在这项双盲、多中心、活性对照的2b期研究中，患有慢性纤维化间质性肺病且表现为进行性表型的患者（定义为尽管接受尼达尼布或吡非尼酮治疗，年预测用力肺活量（%FVC）仍下降≥5%，且%FVC ≥ 50%）被随机分为1:1:1接受帕穆非替尼50毫克、100毫克或对照组（尼达尼布或吡非尼酮）治疗≥6周。

The primary endpoint was the 26-week rate of decline in FVC.

主要终点是26周用力肺活量(FVC)下降率。

measurements_and_main_results

Of the 243 patients randomized, approximately 70% had IPF.

在随机分配的243名患者中，大约70%患有特发性肺纤维化(IPF)。

The 26-week rate of change in FVC was -157.8 mL, -95.9 mL, and -63.6 mL in patients receiving pamufetinib 100 mg, pamufetinib 50 mg, and control, respectively; as such, no clear dose-response relationship was observed.

在接受帕穆非替尼100毫克、帕穆非替尼50毫克和对照组的患者中，26周用力肺活量（FVC）的变化率分别为-157.8毫升、-95.9毫升和-63.6毫升；因此，未观察到明确的剂量-反应关系。

The most frequent adverse eventin the pamufetinib groups was rash, which was mostly mild or moderate in severity.

帕穆非替尼组中最常见的不良事件是皮疹，大多数为轻度或中度。

Conclusions

While the safety profile was acceptable, pamufetinib failed to decelerate FVC decline in patients with CF-ILD with a progressive phenotype who had previously been treated with nintedanib or pirfenidone.

尽管安全性是可以接受的，但帕穆非替尼未能减缓先前接受过尼替达尼或吡非尼酮治疗的具有进展表型的囊性纤维化相关间质性肺病患者的用力肺活量（FVC）下降。

No benefits were demonstrated by switching from standard antifibrotic treatment to pamufetinib monotherapy.Clinical trial registered with the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/en-top; jRCT2051210050).

从标准抗纤维化治疗切换到帕穆非替尼单药治疗并未显示出任何益处。该临床试验已在日本临床试验注册处注册，注册号为jRCT2051210050。