An Open-Label, Dose-Escalation, Non-comparative Clinical Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-245 (JSC BIOCAD, Russia) Administered Intravenously to Subjects With Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Biocad
- 入组人数
- 24
- 试验地点
- 3
- 主要终点
- Proportion of subjects with serious adverse reactions
研究概览
简要总结
The aim of the study is to investigate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of BCD-245 after its single and multiple intravenous infusions at escalating doses in subjects with relapsed/refractory neuroblastoma.
详细描述
The study includes 2 stages: 1) Data collection and safety analysis for the first four subjects 12 years of age and older from Cohort 1 2) Data collection and analysis of safety, pharmacokinetics, pharmacodynamics and immunogenicity in all cohorts (Cohorts 1-4).
The design of this Phase I study is based on standard 3 + 3 design approaches. Cohort 1 includes 4 subjects aged 12 years old and older, and 2 subjects aged 3 years old and older. Cohorts 2-4 include 3-6 subjects aged 3 years and older.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 3 years and older (12 years and older for the first four subjects) at the time of signing the informed consent form
- •Established diagnosis of neuroblastoma (confirmed by the study site laboratory where the subject will be treated) based on: a) histological examination of the tumor tissue (with or without immunohistochemistry) or b) presence of typical tumor agglomerates in the bone marrow and/or meta-iodobenzylguanidine-accumulating focus (foci) and an increase in the level of catecholamine metabolites in serum and/or urine
- •Relapsed or refractory neuroblastoma resistant to the anti-relapse therapy adopted at the study site
- •Satisfactory performance status (>70 on the Lansky or Karnofsky scale)
- •Life expectancy >8 weeks
排除标准
- •Indications for radiation therapy, surgical intervention for the primary disease at screening
- •Isolated CNS relapse of neuroblastoma
- •Planned use of any anticancer drugs concomitantly with BCD-245 in this clinical trial
- •The need for continuous use of anticonvulsants
- •Clinically significant neurological deficit or grade >2 peripheral neuropathy (CTCAE 5.0)
- •The need or probable need for systemic continuous use of glucocorticosteroids or other immunosuppressive drugs
- •Signs of respiratory distress (dyspnea at rest and oxygen saturation <94% without oxygen supplementation)
- •Any severe organ dysfunction (> CTCAE 5.0 severity grade 2) at screening, except for hematological abnormalities.
- •Body weight less than 10 kg.
- •Subject receiving anti-GD2 monoclonal antibody therapy within 6 weeks or less prior to intended study drug infusion
结局指标
主要结局
Proportion of subjects with serious adverse reactions
时间窗: 52 weeks
Proportion of subjects with adverse reactions
时间窗: 52 weeks
Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0
时间窗: 52 weeks
Proportion of therapy discontinuations due to adverse reactions
时间窗: up to 4 weeks
次要结局
- Proportion of subjects with anti-BCD-245 BAbs and NAbs(52 weeks)
- Pre-dose trough concentration (Ctrough)(20 weeks)
- Area under the plasma concentration versus time curve from time zero to t (AUC 0-t)(up to 4 weeks)
- Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-∞)(up to 4 weeks)
- Peak plasma concentration (Cmax)(up to 4 weeks)
- Time of peak plasma concentration (Tmax)(up to 4 weeks)
- Half-life (T1/2)(up to 4 weeks)
- Volume of distribution (Vd)(up to 4 weeks)
- Mean steady-state peak plasma concentration (Cmax)(20 weeks)
- Counts of lymphocytes and CD56+CD16+ (cytokine-secreting and cytotoxic) NK cells(52 weeks)
- Whole blood cytolytic activity test(52 weeks)