Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study.

Nipocalimab是一种新生儿Fc受体阻断剂，在一项2期研究中，与剂量依赖性的总IgG和抗乙酰胆碱受体（AChR）抗体降低相关，并在重症肌无力患者中带来了临床上有意义的改善，体现在肌无力活动日常生活（MG-ADL）量表上。

We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

我们旨在评估nipocalimab在III期研究中的安全性和有效性。

Methods

Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia-Pacific, Europe, and North America.

Vivacity-MG3是一项在亚太、欧洲和北美17个国家的81个具有重症肌无力专业知识的门诊中心进行的III期、随机、双盲、安慰剂对照的III期研究。

Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks.

年龄≥18岁的全身型重症肌无力患者，如果标准治疗（MG-ADL评分≥6）控制不佳，将被随机分配（1:1）接受nipocalimab治疗（首剂30 mg/kg，随后每2周15 mg/kg维持剂量）或安慰剂输注（每2周一次），两种治疗均添加到两组的标准治疗中，持续24周。

Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region.

随机分组按抗体状态、第1天MG-ADL总分和区域进行分层。

The sponsor, investigators, clinical raters, and participants were masked to treatment assignment.

赞助商、研究者、临床评估员和参与者对治疗分配情况均不知情。

The primary endpoint was the difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL total score averaged over weeks 22, 23, and 24 in the intention-to-treatpopulation of patients who were antibody-positive (for AChR, anti-muscle-specific tyrosine kinase [MuSK], or anti-low-density lipoprotein receptor-related protein 4 [LRP4]).

主要终点是基于意向治疗人群中抗体阳性（针对AChR、抗肌肉特异性酪氨酸激酶[MuSK]或抗低密度脂蛋白受体相关蛋白4[LRP4]）患者在第22、23和24周内MG-ADL总分的最小二乘均值变化与基线的差异，比较nipocalimab与安慰剂的效果。

Adverse events were assessed in patients who received at least one dose of study drug.

在至少接受一次研究药物的患者中评估了不良事件。

This study is registered at ClinicalTrials.gov, NCT04951622; the double-blindphase is completed and an open-label extension phase is ongoing.

该研究已在ClinicalTrials.gov注册，编号为NCT04951622；双盲阶段已完成，开放标签扩展阶段正在进行中。

Results

Between July 15, 2021, and Nov 17, 2023, 199 patients were enrolled, and 196 patients received study drug (98 in the nipocalimab group and 98 in the placebo group); of these, 153 (77 in the nipocalimab group and 76 in the placebo group) were antibody-positive.

在2021年7月15日至2023年11月17日期间，共有199名患者被纳入研究，其中196名患者接受了研究药物治疗（nipocalimab组98人，安慰剂组98人）；在这些患者中，153人（nipocalimab组77人，安慰剂组76人）抗体检测呈阳性。

The least-squares mean change in MG-ADL score from baseline to weeks 22, 23, and 24 was -4·70 (SE 0·329) in the nipocalimab group versus -3·25 (0·335) in the placebo group (difference -1·45 [95% CI -2·38 to -0·52]; p=0·0024).

从基线到第22、23和24周，MG-ADL评分的最小二乘平均变化在nipocalimab组为-4.70（标准误0.329），而在安慰剂组为-3.25（标准误0.335）（差异为-1.45 [95%置信区间-2.38至-0.52]；p=0.0024）。

The incidenceof adverse events was similar between groups (82 [84%] of 98 in both the nipocalimab and placebo groups), including infections (42 [43%] of 98 in the nipocalimab group and placebo group) and headache (14 [14%] of 98 in the nipocalimab group and 17 [17%] of 98 in the placebo group).

两组不良事件的发生率相似（nipocalimab组和安慰剂组各有98名患者中的82名[84%]），包括感染（nipocalimab组和安慰剂组各有98名患者中的42名[43%]）和头痛（nipocalimab组有98名患者中的14名[14%]，安慰剂组有98名患者中的17名[17%]）。

Serious adverse events were reported for nine (9%) of 98 patients in the nipocalimab group and 14 (14%) of 98 patients in the placebo group, three of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction).

nipocalimab组有98名患者中的9名（9%）和安慰剂组有98名患者中的14名（14%）报告了严重不良事件，其中三例导致死亡（nipocalimab组：肌无力危象；安慰剂组：心脏骤停和心肌梗死）。

interpretation

Results from the completed double-blindphase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive.

Vivacity-MG3双盲阶段的研究结果支持了将nipocalimab加入标准治疗方案中，作为广泛抗体阳性全身型重症肌无力患者持续疾病控制的安全治疗方法，持续时间可达6个月。

The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab.

正在进行的开放标签扩展阶段应提供nipocalimab长期持续的安全性和有效性的数据。

funding

Janssen Research & Development, LLC, a Johnson & Johnson company.

强生公司的杨森研发有限责任公司