Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial.

Methods

Multicentre, randomised, placebo controlled, phase 2 trial.

一项多中心、随机、安慰剂对照的2期临床试验。

Five hospitals in China, 16 January to 11 June 2024.

2024年1月16日至6月11日，中国五家医院。

45 patients aged ≥18 years with persistent or chronic immune thrombocytopenia who failed to respond to, or relapsed after, glucocorticoid treatment but had previously responded to standard first line treatment.

45名年龄≥18岁的患者，患有持续性或慢性免疫性血小板减少症，对糖皮质激素治疗无反应或治疗后复发，但之前对标准一线治疗有反应。

Patients were randomised to receive intravenous CM313 (16 mg/kg) or placebo weekly for eight weeks.

患者被随机分配接受静脉注射CM313（16 mg/kg）或安慰剂，每周一次，连续八周。

The primary outcome was overall response rate (at least two consecutive platelet counts ≥30×109/L, a minimum doubling from baseline, and no bleeding) at week 8.

主要结果是在第8周时的总反应率（至少连续两次血小板计数≥30×10^9/L，至少是基线的两倍，并且没有出血）。

A secondary outcome was time to the first two consecutive platelet counts ≥50×109/L.

次要结果指标是首次连续两次血小板计数达到或超过50×10^9/L的时间。

Results

Of 56 patients screened, 45 were randomised to receive CM313 (n=30) or placebo (n=15).

在56名筛查的患者中，有45名被随机分配接受CM313（n=30）或安慰剂（n=15）。

At week 8, the overall response rate was higher in the CM313 group (83%; 25/30) compared with placebo group (20%; 3/15): difference 63.3% (95% confidence interval33.7% to 81.3%; P<0.001).

在第8周时，CM313组的总缓解率（83%；25/30）高于安慰剂组（20%；3/15）：差异为63.3%（95%置信区间33.7%至81.3%；P<0.001）。

The median time to a platelet count of ≥50×109/L was one week in the CM313 group but was not reached in the placebo group (P<0.001).

CM313组达到血小板计数≥50×10^9/L的中位时间是一周，而在安慰剂组中未达到（P<0.001）。

The median cumulative response duration for platelet counts ≥50×109/L was 18 weeks in the CM313 group versus three weeks in the placebo group (P=0.004).

CM313组血小板计数≥50×10^9/L的中位累积反应持续时间为18周，而安慰剂组为三周（P=0.004）。

Treatment emergent adverse events occurred in 87% (26/30) of patients in the CM313 group and 80% (12/15) in the placebo group, with infusion related reactions and petechiae being the most common.

CM313组87%（26/30）的患者和安慰剂组80%（12/15）的患者出现了治疗相关的不良事件，其中输液相关反应和瘀点是最常见的。

Conclusions

CM313 showed a favourable safety profile and encouraging efficacy in adults with persistent or chronic primary immune thrombocytopenia, characterised by rapid increase in platelet count, sustained platelet responses, and manageable adverse events.

CM313在成人持续性或慢性原发性免疫性血小板减少症患者中显示出良好的安全性和令人鼓舞的疗效，其特点是血小板计数迅速增加，血小板反应持续，不良事件可管理。

trial_registration

ClinicalTrials.gov NCT06199089.

ClinicalTrials.gov NCT06199089。