Avatrombopag for the treatment of children and adolescents with immune thrombocytopenia (AVA-PED-301): a multicentre, randomised, double-blind, placebo-controlled, phase 3b study.

The aim of this study was to assess the efficacy, safety, tolerability, and pharmacokinetic and pharmacodynamic profile of avatrombopag for children and adolescents with persistent and chronic primary ITP.

本研究旨在评估阿伐曲波帕对持续和慢性原发性ITP儿童和青少年的疗效、安全性、耐受性以及药代动力学和药效学特征。

Methods

AVA-PED-301 is a global, multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 3b study.

AVA-PED-301是一项全球多中心、随机、双盲、安慰剂对照、平行组、3b期研究。

Children and adolescents aged ≥1 to <18 years with a confirmed diagnosis of primary ITP for at least 6 months and an insufficient response to a previous treatment were randomly assigned (3:1) to avatrombopag (aged ≥6 years: 20 mg oral tablet once daily; aged ≥1 to <6 years: 10 mg oral suspension once daily) or matching placebo.

年龄在≥1岁至<18岁的儿童和青少年，经确诊为原发性ITP至少6个月且对先前治疗反应不足，被随机分配（3:1）接受阿瓦特罗帕格（≥6岁：每日一次口服20毫克片剂；≥1岁至<6岁：每日一次口服10毫克悬浮液）或匹配安慰剂。

Doses were titrated to maintain a platelet count of 50-150 × 109 cells per L.

剂量被调整以维持血小板计数在50-150 × 10^9细胞/L之间。

The core-phase (12-week double-blindtreatment period) full analysis set included all randomly assigned patients; efficacy analysis was performed based on randomised study drug.

核心阶段（12周的双盲治疗期）的完整分析集包括所有随机分配的患者；基于随机化的研究药物进行了疗效分析。

The safety analysis set included all patients who received at least one dose of study drug in each study phase.

安全性分析集包括在每个研究阶段接受了至少一剂研究药物的所有患者。

The primary endpoint was durable platelet response (proportion of patients with at least six out of eight weekly platelet counts ≥50 × 109 cells per L during the last 8 weeks of the 12-week treatment period in the absence of rescue therapy); the alternative primary endpoint was platelet response (proportion of patients with at least two consecutive platelet assessments ≥50 × 109 cells per L over the 12-week treatment period in the absence of rescue therapy).

主要终点是持续的血小板反应（在没有救援治疗的情况下，至少在12周治疗期的最后8周内，每周的血小板计数至少有六次≥50 × 10^9细胞/L的患者比例）；次要主要终点是血小板反应（在没有救援治疗的情况下，12周治疗期内至少有两次连续的血小板评估≥50 × 10^9细胞/L的患者比例）。

The trial core phase is complete and was registered with ClinicalTrials.gov (NCT04516967).

试验核心阶段已完成，并已在ClinicalTrials.gov上注册（NCT04516967）。

Results

Between March 2, 2021, and Aug 2, 2023, 83 children were screened, with 75 randomly assigned to avatrombopag (n=54; 24 [44%] female; 48 [89%] White) or placebo (n=21; 12 [57%] female; 15 [71%] White). 15 (28%) patients in the avatrombopag group met the primary endpoint of durable platelet response versus no (0%) patients in the placebo group (difference in response rate 28% [95% CI 16-40]; p=0·0077); 44 (81%) patients in the avatrombopag group met the alternative primary endpoint of platelet response versus no (0%) patients in the placebo group (difference in response rate 81% [71-92]; p<0·0001).

在2021年3月2日至2023年8月2日期间，共有83名儿童接受了筛查，其中75名被随机分配接受阿伐曲波帕治疗（n=54；女性24名[44%]；白人48名[89%]）或安慰剂（n=21；女性12名[57%]；白人15名[71%]）。

The most common adverse events across treatment groups were petechiae (n=20), epistaxis (n=16), and headache (n=14).

各治疗组中最常见的不良事件是瘀点（n=20），鼻出血（n=16）和头痛（n=14）。

Serious adverse events were reported in five (9%) patients in the avatrombopag group and one (5%) patient in the placebo group.

在阿瓦曲波帕组中有五名（9%）患者报告了严重不良事件，在安慰剂组中有一名（5%）患者报告了严重不良事件。

No deaths, thromboembolic events, or grade 3 or higher bleeding events were reported.

未报告死亡、血栓栓塞事件或3级或更高级别的出血事件。

interpretation

Avatrombopag is an effective oral treatment for children and adolescents with ITP for at least 6 months and has a reassuring safety profile in the paediatric population.

Avatrombopag 是一种有效的口服治疗药物，适用于至少6个月的儿童和青少年ITP患者，并且在儿科人群中具有令人安心的安全性。

Avatrombopag could provide an important treatment option for paediatric ITP.

Avatrombopag 可能为儿童免疫性血小板减少症(ITP)提供一个重要治疗选择。

funding

Sobi.

Sobi 公司。