Deupirfenidone compared with pirfenidone and placebo in idiopathic pulmonary fibrosis (ELEVATE-IPF): a phase 2b randomized placebo-controlled trial.

Background

To evaluate the efficacy and safety of deupirfenidone compared with placebo and pirfenidone in patients with IPF.

评估 deupirfenidone 与安慰剂和吡非尼酮在 IPF 患者中的疗效和安全性比较。

Methods

Patients were randomized 1:1:1:1 to deupirfenidone 550 mg TID, deupirfenidone 825 mg TID, pirfenidone 801 mg TID, or placebo.

患者按1:1:1:1的比例随机分配至每日三次的550 mg deupirfenidone、825 mg deupirfenidone、801 mg pirfenidone或安慰剂治疗。

The primary endpoint was the rate of change in forced vital capacity (FVC) for the combined arms of deupirfenidone versus placebo at 26 weeks.

主要终点是26周时，deupirfenidone联合治疗组与安慰剂组在用力肺活量（FVC）变化率上的差异。

The primary and secondary analyses used Bayesian and frequentist approaches, respectively.

主要分析和次要分析分别使用了贝叶斯方法和频率论方法。

measurements_and_main_results

A total of 257 patients with IPF were randomized, and the proportion on treatment at the end of the study was 80.0%, 68.3%, 64.6%, and 78.1% for the placebo, pirfenidone, deupirfenidone 550 mg, and deupirfenidone 825 mg arms, respectively.

共有257名特发性肺纤维化(IPF)患者被随机分配，研究结束时，安慰剂组、吡非尼酮组、550毫克度匹非尼酮组和825毫克度匹非尼酮组的治疗比例分别为80.0%、68.3%、64.6%和78.1%。

Posterior mean change in FVC for placebo was -110.71 mL (95% credible interval (CI), -148.75, -70.98), and for the combined deupirfenidone arms was -48.42 mL (95% CI, -87.66, -9.04) with a posterior mean difference of 62.29 mL (95% CI l, -6.13, 115.73; posterior probability, 0.985).

安慰剂组的FVC后验平均变化为-110.71毫升（95%可信区间（CI），-148.75，-70.98），而联合度匹非尼酮组为-48.42毫升（95% CI，-87.66，-9.04），后验平均差异为62.29毫升（95% CI，-6.13，115.73；后验概率，0.985）。

Using a frequentist approach, the adjusted mean change in FVC for the placebo arm was -112.5 mL (95% CI, -167.2, -57.8), and for the deupirfenidone 825 mg arm was -21.5 mL (95% CI, -78.2, 35.1); the adjusted mean difference was 91.0 mL (95% CI, 12.2, 169.7; P = .02).

使用频率主义方法，安慰剂组的调整后平均FVC变化为-112.5毫升（95% CI，-167.2，-57.8），度匹非尼酮825毫克组为-21.5毫升（95% CI，-78.2，35.1）；调整后平均差异为91.0毫升（95% CI，12.2，169.7；P = .02）。

The most common adverse events for each active treatment arm were gastrointestinal.

每个活性治疗组最常见的不良事件是胃肠道相关。

Conclusions

In patients with IPF, treatment with deupirfenidone slowed lung disease progression over 26 weeks.

在特发性肺纤维化(IPF)患者中，使用去匹非尼酮治疗26周可减缓肺部疾病的进展。

trial_registration

Clinicaltrials.gov number NCT05321420.

临床试验注册号 NCT05321420。