A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia.

Available therapies are ineffective in at least 20% of cases.

现有治疗方法在至少20%的病例中无效。

Mezagitamab is an anti-CD38 antibody that targets plasma cells, plasmablasts, and natural killer cells.

Mezagitamab 是一种靶向浆细胞、浆母细胞和自然杀伤细胞的抗 CD38 抗体。

Methods

We conducted this multicenter, double-blind, randomized, placebo-controlledtrial to assess the safety and efficacy of mezagitamab at a dose of 100 mg, 300 mg, or 600 mg, as compared with placebo, administered subcutaneously once weekly for 8 weeks in adults with persistent or chronic ITP (mean platelet count on ≥2 measurements, <30,000 per microliter).

我们进行了一项多中心、双盲、随机、安慰剂对照试验，以评估与安慰剂相比，每周一次皮下注射 100 mg、300 mg 或 600 mg 的 mezagitamab 的安全性和有效性，连续 8 周，用于治疗持续或慢性免疫性血小板减少症（ITP）成人患者（在≥2次测量中，平均血小板计数<30,000/微升）。

The primary end point was adverse events.

主要终点是不良事件。

A key secondary efficacy end point was a platelet response (defined by a platelet count of ≥50,000 per microliter and ≥20,000 per microliter above the baseline value) on at least two visits at any time through week 16.

一个关键的次要疗效终点是血小板反应（定义为血小板计数≥50,000每微升，并且至少比基线值高出20,000每微升），在第16周的任何时间至少在两次随访中出现。

Results

In the combined mezagitamab groups (28 participants), the mean age was 50 years (range, 24 to 88) and the mean number of previous ITP therapies was 4 (range, 1 to 9); in the combined placebo groups (13 participants), the mean age was 39 years (range, 20 to 65) and the mean number of previous ITP therapies was 4 (range, 1 to 13).

在联合mezagitamab组（28名参与者）中，平均年龄为50岁（范围，24至88岁），平均既往ITP治疗次数为4次（范围，1至9次）；在联合安慰剂组（13名参与者）中，平均年龄为39岁（范围，20至65岁），平均既往ITP治疗次数为4次（范围，1至13次）。

The mean baseline platelet count was 19,100 and 17,300 per microliter, respectively.

基线血小板计数的平均值分别为每微升19,100和17,300。

Adverse events were reported in 19 of 28 participants (68%) in the combined mezagitamab groups and in 9 of 13 participants (69%) in the combined placebo groups; adverse events of grade 3 or higher in 5 of 28 participants (18%) and in 3 of 13 participants (23%), respectively; and serious adverse events in 4 of 28 participants (14%) and in 1 of 13 participants (8%).

在联合mezagitamab组的28名参与者中，有19人（68%）报告了不良事件，在联合安慰剂组的13名参与者中，有9人（69%）报告了不良事件；在mezagitamab组中有5人（18%）和在安慰剂组中有3人（23%）分别报告了3级或更高级别的不良事件；在mezagitamab组中有4人（14%）和在安慰剂组中有1人（8%）分别报告了严重不良事件。

Through week 16, a platelet response was observed in 10 of 11 participants (91%) in the mezagitamab 600-mg group and in 3 of 13 participants (23%) in the combined placebo groups.

截至第16周，mezagitamab 600-mg组的11名参与者中有10人（91%）观察到血小板反应，在联合安慰剂组的13名参与者中有3人（23%）观察到血小板反应。

Conclusions

Treatment with mezagitamab led to increased platelet counts, with a safety profile that appeared to be similar to that of placebo among participants with persistent or chronic ITP.

Mezagitamab治疗导致血小板计数增加，其安全性特征似乎与持续性或慢性免疫性血小板减少症患者的安慰剂相似。

(Funded by Takeda Development Center Americas; ClinicalTrials.gov number, NCT04278924.).

(该研究由武田开发中心美洲资助；ClinicalTrials.gov注册号，NCT04278924。)