Efficacy and safety of anrikefon in patients with pruritus undergoing haemodialysis: multicentre, double blind, randomised placebo controlled phase 3 trial.

Methods

Multicentre, double blind, randomised placebo controlled phase 3 trial.

多中心、双盲、随机、安慰剂对照的III期临床试验。

50 centres in China, June 2022 to June 2024.

在中国的50个中心，研究时间跨度为2022年6月至2024年6月。

652 patients with moderate to severe CKD associated pruritus undergoing haemodialysis were screened: 545 were randomly assigned (1:1 ratio) to receive either anrikefon (n=275) or placebo (n=270).

共有652名中度至重度慢性肾脏病相关瘙痒症患者接受血液透析筛查：其中545名患者按1:1的比例随机分配，接受anrikefon治疗（n=275）或安慰剂（n=270）。

Intravenous anrikefon (0.3 μg/kg body weight) or placebo three times weekly for 12 weeks, followed by an optional open label extension phase with anrikefon treatment for 40 weeks.

静脉注射阿尼瑞芬（0.3 μg/kg体重）或安慰剂，每周三次，持续12周，随后是一个可选的开放标签扩展阶段，阿尼瑞芬治疗持续40周。

The primary endpoint was the percentage of patients achieving at least a 4 point reduction in weekly mean 24 hour worst itching intensity numerical rating scale (WI-NRS) score from baseline to week 12.

主要终点是至少有4分的改善，即从基线到第12周，患者每周平均24小时最严重瘙痒强度数值评分（WI-NRS）的百分比。

Secondary outcomes were the percentage of patients achieving at least a 3 point reduction in weekly mean WI-NRS score from baseline to week 12, as well as changes in itch related quality of life from baseline using the Skindex-10 and 5-D itch scales.

次要结果是患者从基线到第12周每周平均WI-NRS评分至少降低3分的百分比，以及使用Skindex-10和5-D瘙痒量表从基线开始的瘙痒相关生活质量的变化。

The change in itch related quality of life from baseline to week 40 of open label treatment was also reported using the 5-D itch scale.

在开放标签治疗的第40周，还报告了使用5-D瘙痒量表从基线到第40周瘙痒相关生活质量的变化。

The safety of anrikefon was evaluated throughout the trial.

整个试验期间对安瑞克芬的安全性进行了评估。

Results

243/275 (88%) patients in the anrikefon group and 254/270 (94%) in the placebo group completed the 12 week double blind treatment. 443 subsequently entered the 40 week open label extension phase. 37% of patients in the anrikefon group showed at least a 4 point reduction in WI-NRS score at week 12 compared with 15% in the placebo group (P<0.001).

在安瑞克芬组中，243/275（88%）的患者和在安慰剂组中，254/270（94%）的患者完成了12周的双盲治疗。随后，443名患者进入了40周的开放标签扩展阶段。在第12周时，安瑞克芬组中有37%的患者显示至少有4分的WI-NRS评分降低，而在安慰剂组中这一比例为15%（P<0.001）。

The percentage of patients with at least a 3 point reduction in WI-NRS score from baseline to week 12 was 51% in the anrikefon group compared with 24% in the placebo group (P<0.001).

从基线到第12周，至少减少3分WI-NRS评分的患者比例在anrikefon组为51%，而在安慰剂组为24%（P<0.001）。

The anrikefon group showed significant improvements in itch related quality of life (mean change from baseline in 5-D itch scale -5.3 v -3.1, P<0.001 and in Skindex-10 scale -15.2 v -9.3, P<0.001).

anrikefon组在瘙痒相关生活质量方面显示出显著改善（基线平均变化在5-D瘙痒量表为-5.3对比-3.1，P<0.001；在Skindex-10量表为-15.2对比-9.3，P<0.001）。

Anrikefon also showed sustained long term efficacy during the open label extension phase at week 40, with persistent improvement in quality of life scores on the 5-D itch scale.

在第40周的开放标签扩展阶段，Anrikefon也显示出持续的长期疗效，5-D瘙痒量表上的生活质量评分持续改善。

Mild to moderate dizziness was more common in the anrikefon group than placebo group but without evident clinical consequences.

与安慰剂组相比，轻度至中度头晕在Anrikefon组中更为常见，但没有明显的临床后果。

Conclusions

In patients with moderate to severe pruritus undergoing haemodialysis, anrikefon was found to be safe and resulted in a noticeable reduction in itch intensity and an improvement in itch related quality of life.

在进行血液透析的中度至重度瘙痒患者中，发现anrikefon是安全的，并且显著降低了瘙痒强度，改善了与瘙痒相关的生活质量。

trial_registration

ClinicalTrials.gov NCT05135390.

ClinicalTrials.gov NCT05135390。