An Open Study of the Safety and Pharmacokinetics of GNR-038 in Sequential Dose-increase Cohorts in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AO GENERIUM
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of participants with Adverse Events
研究概览
简要总结
It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-038.
详细描述
Hereditary angioedema (HAE) is a rare potentially life-threatening genetically determined disease associated with a deficiency or impairment of C1 esterase inhibitor (C1 inhibitor) functional activity. Main clinical manifestations of HAE are recurrent mucous membranes edema and localization of the derma deep layers. Attack persist from several hours to several days and disappear without a trace in most cases, without additional therapy.
The prevalence of the disease in the world is from 1:10 000 to 1: 150 000. The plasma/recombinant C1 inhibitor use to compensate for its deficiency or insufficient functional activity in patients with HAE is recommended both for severe and for long-term and short-term (before surgical interventions and dental manipulations) prophylaxis.
GNR-038 is a recombinant C1 inhibitor (rhC1-inh), which is a complete structural and functional analogue of the plasma C1 inhibitor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged 18 to 50 (inclusive) at the time of signing the Informed Consent Form.
- •Body mass index (BMI) in the range from 18.5 to 30 kg / m2, body weight from 50 to 90 kg.
- •The diagnosis is "healthy" according to the data of clinical and biochemical blood tests, urinalysis, results of physical examination, measurement of vital signs, results of electrocardiography.
- •Availability of written informed consent obtained from the volunteer prior to any research-related procedures performance.
- •Consent to follow the adequate contraceptive methods.
排除标准
- •Known hypersensitivity to the components of the study drug;
- •Burdened allergic history;
- •Standard laboratory and instrumental parameters values are outside the normal range;
- •Cardiovascular, bronchopulmonary, neuroendocrine systems chronic diseases, as well as gastrointestinal tract, liver, kidneys, hematopoietic, immune systems diseases, mental illness;
- •Diseases and conditions associated with thrombosis (myocardial infarction, transient ischemic attacks, deep and superficial vein thrombosis, pulmonary embolism) less than 6 months before the screening period start, as well as an increased risk of arterial or venous thrombosis according to the investigator opinion.
- •Infection with human immunodeficiency virus (HIV), hepatitis B and C;
- •Acute infectious diseases less than 4 weeks prior to the Screening Visit;
- •Regular medication intake less than 2 weeks prior to the Screening Visit;
- •For women - the hormonal contraceptives use or hormone replacement therapy for 3 months before the screening period start;
- •Systolic pressure less than 100 mmHg or above 140 mmHg; diastolic pressure less than 70 mmHg or above 90 mmHg; pulse rate less than 60 beats/min or more than 90 beats/min;
- •Blood donation (450 ml of blood or plasma and more) less than 3 months before the Screening Visit;
- •Participation in clinical trials less than 3 months before the Screening Visit;
- •More than 10 alcohol units intake per week (1 unit of alcohol is equivalent to 1/2 liter of beer, 200 ml of wine or 50 ml of ethanol) OR anamnestic information about alcoholism, detection of ethanol in exhaled air;
- •Drug addiction, substance abuse, positive urine test for the content of potent and narcotic drugs;
- •Smoking more than 10 cigarettes a day;
- •Pregnancy or breastfeeding;
- •Other reasons that prevent the volunteer from study participating or create an unreasonable risk in the investigator opinion.
研究组 & 干预措施
GNR-038, 25 МЕ/kg
Recombinant C1-esterase (25 ME/kg) inhibitor intravenous infusion
干预措施: GNR-038, 25 МЕ/kg (Biological)
GNR-038, 50 МЕ/kg
Recombinant C1-esterase (50 ME/kg) inhibitor intravenous infusion
干预措施: GNR-038, 50 МЕ/kg (Biological)
GNR-038, 100 МЕ/kg
Recombinant C1-esterase (100 ME/kg) inhibitor intravenous infusion
干预措施: GNR-038, 100 МЕ/kg (Biological)
结局指标
主要结局
Number of participants with Adverse Events
时间窗: 28 Days
Adverse events, Laboratory tests, Vital signs, Physical examination, 12-lead electrocardiogram, Allergic associated reaction, Infusion associated reaction, Antidrug antibody.
次要结局
- Area under the plasma concentration versus time curve (AUC)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
- Mean retention time (MRT)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
- Elimination rate constant (Kel)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
- Peak Plasma Concentration (Cmax)(45, 30 and 15 minutes before GNR-038 infusion; 0, 15, 30 minutes, 1, 2, 4, 8,12,16, 24, 48, 72, 96, 120,144 and 168 hours after GNR-038 infusion)
- Half-life (T1/2)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
- Overall clearance (Cl)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
- Kinetic volume of distribution (Vz)(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)