A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GR2001 Injection in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 202
- 试验地点
- 1
- 主要终点
- Incidence of AEs(Phase I)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and Immunogenicity characteristics of GR2001 and compare the anti-tetanus neutralizing antibody titers of GR2001 with human tetanus immunoglobulin (HTIG)in healthy adult subjects.
详细描述
This is a Multicentre, Randomized, Double-Blind, Placebo-Controlled, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of GR2001 Injection in Healthy Subjects.
In the phase I part of the study, a total of 94 healthy subjects will be enrolled. The 94 healthy adult subjects will be enrolled into 7 cohorts sequentially. Each participant will receive a single IM dose of GR2001 or placebo or HTIG according to the cohort in which they were enrolled. After injection (Day 0), participants will remain in the study site for observation up to Day 1. The phase I part will last for 105 days following the assessments of safety, PK, PD and ADA.
In the phase II part of the study, a total of 108 healthy subjects will be enrolled. The 108 healthy subjects will be randomly assigned to the experimental group and the control group based on a ratio of 1:1:1:2:2:2.The phase II part will last for 105 days following the assessments of safety, PK, PD and ADA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double Blind
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female, 18-60 years of age (both inclusive);
- •Body mass index within 18.0-27.0 kg/m2 (both inclusive);
- •Subjects including partners are willing to voluntarily take effective contraceptive measures from screening to 6 months after the last study drug administration.
- •Completed written informed consent process, signed the informed consent forms and Agreed to complete all follow-ups.
排除标准
- •History or evidence of severe drug or excipient allergy;
- •History or evidence of tetanus infection;
- •Inoculation of tetanus vaccine within 10 years;
- •History or evidence of any other acute or chronic disease；
- •Known or suspected history of drug abuse；
- •Positive outcome for Tetanus-antibody IgG test;
- •Nursing mothers or pregnant women.
研究组 & 干预措施
Cohort 1 GR2001 0.01mg/kg/placebo
Four subjects will be randomly assigned to receive either GR2001 or placebo at a 3:1 ratio (i.e. 3 subjects receive GR2001 and 1 with placebo).
干预措施: Placebo (Biological)
Cohort 2 GR2001 0.02mg/kg/placebo
Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo).
干预措施: Placebo (Biological)
Cohort 3 GR2001 0.05mg/kg/placebo/HTIG
24 subjects will be randomly assigned to receive GR2001 or placebo or HTIG(250IU) at a 1:1:1 ratio (i.e. 8 subjects receive GR2001, 8 with placebo and 8 with HTIG).
干预措施: Placebo (Biological)
Cohort 3 GR2001 0.05mg/kg/placebo/HTIG
24 subjects will be randomly assigned to receive GR2001 or placebo or HTIG(250IU) at a 1:1:1 ratio (i.e. 8 subjects receive GR2001, 8 with placebo and 8 with HTIG).
干预措施: HTIG (Biological)
Cohort 4 GR2001 0.1mg/kg/placebo
Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo).
干预措施: Placebo (Biological)
Cohort 5 GR2001 0.2mg/kg/placebo
Ten subjects will be randomly assigned to receive either GR2001 or placebo at a 4:1 ratio (i.e. 8 subjects receive GR2001 and 2 with placebo).
干预措施: Placebo (Biological)
Cohort 6 GR2001 0.1mg/kg/placebo
Eighteen subjects will be randomly assigned to receive either GR2001 or placebo at a 2:1 ratio (i.e. 12 subjects receive GR2001 and 6 with placebo) followed by a dose of Tetanus Toxoid（TT） on Day0.
干预措施: Placebo (Biological)
Cohort 7 GR2001 0.2mg/kg/placebo
Eighteen subjects will be randomly assigned to receive either GR2001 or placebo at a 2:1 ratio (i.e. 12 subjects receive GR2001 and 6 with placebo) followed by a dose of Tetanus Toxoid（TT） on Day0.
干预措施: Placebo (Biological)
Cohort 8 GR2001 0.1mg/kg/ GR2001 0.2mg/kg/ HTIG
Thirty six subjects will be randomly assigned to receive GR2001(0.1mg/kg) or GR2001(0.2mg/kg) or HTIG(250IU) at a 1:1:1 ratio (i.e. 12 subjects receive GR2001(0.1mg/kg), 12 with GR2001(0.2mg/kg) and 12 with HTIG).
Seventy two subjects will be randomly assigned to receive GR2001(0.1mg/kg) or GR2001(0.2mg/kg) or HTIG(250IU) at a 1:1:1 ratio (i.e. 24 subjects receive GR2001(0.1mg/kg), 24 with GR2001(0.2mg/kg) and 24 with HTIG) followed by one dose of Tetanus Toxoid（TT） on Day0 and Day28.
干预措施: HTIG (Biological)
结局指标
主要结局
Incidence of AEs(Phase I)
时间窗: Up to 105 days
Number of participants with treatment-related adverse events or serious adverse events.
Tetanus-antibody titer(Phase II)
时间窗: 24 hours post administration
Tetanus-antibody titer post administration.
次要结局
- Incidence of ADA(Phase I/II)(Up to 105 days)
- Incidence of AEs(Phase II)(Up to 105 days)
- Peak plasma concentration(Cmax)(Up to 105 days)
- Area under the plasma concentration versus time curve (AUC)(Up to 105 days)
- Apparent total body clearance (CL/F)(Up to 105 days)
- Time of maximum plasma concentration (Tmax)(Up to 105 days)
- Tetanus-antibody titer(Phase I/II)(Up to 105 days)
- Apparent volume of distribution (Vd/F)(Up to 105 days)
- The elimination rate constant (Kel)(Up to 105 days)
- Mean Residence Time (MRT)(Up to 105 days)
- Terminal half-life (T1/2)(Up to 105 days)