Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: A Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial.

Current therapies may slow disease progression but do not clear existing deposits.

目前的治疗方法可能可以减缓疾病进展，但无法清除已有的沉积物。

Coramitug is a humanized monoclonal antibody that targets misfolded transthyretin, designed to promote clearance of transthyretin amyloid through antibody-mediated phagocytosis.

Coramitug是一种针对错误折叠的甲状腺转运蛋白的人源化单克隆抗体，旨在通过抗体介导的吞噬作用促进甲状腺转运蛋白淀粉样蛋白的清除。

Methods

This phase 2, double-blind, placebo-controlledtrial randomized participants with transthyretin amyloidosis with cardiomyopathy to receive infusions every 4 weeks of either coramitug at 2 dosages (10 mg/kg or 60 mg/kg) or placebo in a 1:1:1 ratio for 52 weeks.

这项第二阶段、双盲、安慰剂对照试验将患有甲状腺转运蛋白淀粉样变性并伴有心肌病的参与者随机分配，每4周接受一次Coramitug的输注，剂量为10 mg/kg或60 mg/kg，或安慰剂，按照1:1:1的比例进行，持续52周。

The primary end points were the change from baseline to week 52 in the 6-minute walk test and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels.

主要终点是基线至第52周6分钟步行测试和NT-proBNP（N末端前体B型利钠肽）水平的变化。

Safety was assessed for up to 64 weeks by assessing treatment-emergent adverse events, all-cause mortality, and number of cardiovascular events (comprising hospitalization caused by cardiovascular events or urgent heart failure visits).

安全性通过评估治疗后出现的不良事件、全因死亡率以及心血管事件的数量（包括因心血管事件住院或紧急心力衰竭就诊）来评估，评估时间最长可达64周。

Results

In total, 104 participants (median age, 77 years; 93% men; 84% New York Heart Association class II; 13% with variant transthyretin amyloidosis with cardiomyopathy) were randomized and dosed: 34 to 10 mg/kg of coramitug, 35 to 60 mg/kg of coramitug, and 35 to placebo.

共有104名参与者（中位年龄77岁；93%为男性；84%为纽约心脏病协会II级；13%患有变体甲状腺素淀粉样变性心肌病）被随机分组并给予剂量：34人接受10 mg/kg的coramitug，35人接受60 mg/kg的coramitug，另外35人接受安慰剂。

Median NT-proBNP was 1985 pg/mL (interquartile range, 1224, 3406).

NT-proBNP的中位数为1985 pg/mL（四分位数范围，1224, 3406）。

In total, 90% of participants were receiving disease-modifying therapy; 84% were treated with tafamidis and 7 (6.7%) with transthyretin silencers (patisiran, n=4; vutrisiran, n=3).

总体而言，90%的参与者正在接受疾病修饰性治疗；84%接受了他法米迪治疗，7名（6.7%）接受了甲状腺素抑制剂治疗（帕替司兰，n=4；维特里斯兰，n=3）。

From baseline to week 52, 60 mg/kg of coramitug significantly reduced NT-proBNP levels compared with placebo (-48% [95% CI, -65% to -22%]; P=0.0017).

从基线到第52周，60 mg/kg的coramitug与安慰剂相比显著降低了NT-proBNP水平（-48% [95% 置信区间, -65% 至 -22%]；P=0.0017）。

The change in 6-minute walk test from baseline to week 52 was not statistically different from placebo with either dose.

从基线到第52周的6分钟步行测试的变化与安慰剂相比，无论剂量如何，均无统计学差异。

Coramitug (60 mg/kg) was associated with improved functional echocardiographic parameters and was well tolerated.

Coramitug (60 mg/kg) 与改善的功能性超声心动图参数相关，并且耐受性良好。

Conclusions

This phase 2 trial showed that coramitug, an antibody targeting misfolded transthyretin in transthyretin amyloidosis with cardiomyopathy, was well tolerated and, at a dose of 60 mg/kg, resulted in a statistically significant reduction in NT-proBNP, a validated marker of disease progression, with no statistically significant effect on 6-minute walk test within 52 weeks.

这项2期试验显示，针对心脏型转甲状腺素淀粉样变性中错误折叠的转甲状腺素的抗体coramitug，在60 mg/kg剂量下耐受性良好，并且在52周内导致NT-proBNP（疾病进展的验证性标志物）统计学上显著降低，但对6分钟步行测试没有统计学上显著的影响。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05442047.

URL: https://www.clinicaltrials.gov; 唯一标识符: NCT05442047.