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A Single Dose Escalation Study of PCSK9 Inhibitor (JS002) in Health Subjects

2019年12月11日 更新者:Shanghai Junshi Bioscience Co., Ltd.

A Randomized, Double-blind, Placebo-controlled, Single-dose Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JS002 (Recombinant Humanized Anti-PCSK9 Monoclonal Antibody) Injection in Healthy Subjects.

JS002 is a recombinant humanized Anti- PCSK9 monoclonal antibody; This is a phase Ia, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single subcutaneous injection of JS002 in healthy subjects.

In this study, the dose ascending design includes five dose level cohorts (15 mg, 50 mg, 150 mg, 300 mg, and 450 mg) administered by subcutaneous injection, and three intravenous administration cohorts (15 mg, 150 mg, and 450 mg). Each cohort will enroll 8 to 12 subjects (distribution of study drug and placebo in a 3:1 ratio).

The duration of the study is 84-day per subjects.

研究概览

地位

完全的

研究类型

介入性

注册 (实际的)

84

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Beijing
      • Beijing、Beijing、中国、100020
        • Fuwai Hospital Chinese Academy of Medical Sciences

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 45年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Healthy men or women aged 18 to 45 years old at screening visit;
  2. Have the ability to read and understand, volunteer to participate in the study, and signed written informed consent.
  3. The body mass index (BMI) at screening visit was in the range of 18 to 30 kg/m2 (inclusive) and the body weight ≥ 50 kg.
  4. The sitting blood pressure ≥90/60 mmHg and <140/90 mmHg at screening visit.
  5. Serum LDL-C level ≥ 70 mg/dL (1.8 mmol/L) and < 190 mg/dL (4.9 mmol/L) at screening visit.
  6. Serum Triglyceride (TG) level < 250 mg/dL (2.8 mmol/L) at screening visit.
  7. No fertility [female: documented hysterectomy, bilateral oophorectomy, tubal ligation or other female permanent sterilization, or menopause (menopause for more than one year)], or those with fertility are willing to take, during the entire study period, strict and effective contraceptive measures, in addition, female subjects with fertility should have a negative blood/urine pregnancy test at screening visit.

Exclusion Criteria:

  1. Subjects who meet any of the following criteria will be excluded from the study:
  2. Evolocumab and/or Alirocumab, or other targeted drugs to PCSK9, has been used at any time.
  3. Any therapeutic or research biological agents has been used during the first 6 months of baseline/random (Day 0).
  4. Participated in any clinical study within 3 months prior to baseline/random (Day 0).
  5. Any drug or health supplement that affects blood lipids or lipid metabolism during the first 30 days of baseline/random (Day 0), including but not limited to: Probucol, statins (e.g. Atorvastatin, Rosuvastatin, etc.), cholesterol absorption inhibitors (such as Ezetimibe), bile acid sequestrants (such as Cholestyramine), red yeast and hawthorn preparations, fibrates, high-purity fish oil preparations (or omega-fatty acids ≥ 1000 mg / day) and niacin preparation (nicotinic acid ≥ 50 mg), etc.
  6. Start a new intense exercise or diet control within 30 days of random (Day 0) or major changes to previous diet and lifestyle (including exercise, smoking and drinking). The following conditions occur before the baseline/random (Day 0) 1 day (ie Day-1) need to be excluded:

    • Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) (Note: related to exercise), or
    • Urinary cotinine is positive, or
    • Positive alcohol saliva test.
  7. Previous or concomitant diseases (such as nephrotic syndrome, liver disease, diabetes, hypothyroidism, etc.) or any clinically significant abnormalities found in physical examinations, laboratory tests, and electrocardiograms, which would make the subject unsuitable for this study.
  8. The medical history or clinical evidence indicates that the subject had severe acute or chronic disease (including not limited to: heart, kidney, nerves, endocrine, blood, immunity, infection, metabolic disorders, etc.), and the disease has not been controlled, which may confuse the outcome of the study or put the subject at risk judged by the investigator, The following situations need to be excluded:

    • had major surgery in the last 6 months, or
    • has been hospitalized (e.g. infection) in the last 3 months, or
    • donated blood or blood loss ≥500 mL in the past 3 months, or
    • has used any prescription or over-the-counter drugs in the past 1 month.
  9. Transplantation History of organs (such as heart, lung, liver, kidney, etc.) Malignant tumors history, except for cervical carcinoma in situ or surgically resected skin cancer (basal cells and squamous epithelial cells) for more than 5 years.
  10. Drug abuse or alcohol dependence in the past 1 year.
  11. HIV infection, or HIV antibody positive at screening visit.
  12. Syphilis infection, or serotonin antibody (TPPA) positive at screening visit.
  13. Hepatitis B surface antigen (HBsAg) was positive at screening visit.
  14. Hepatitis C virus (HCV) antibody was positive at screening visit.
  15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 times the upper limit of normal (ULN).
  16. Allergy history to mammalian-derived biological agents, including monoclonal antibodies.
  17. Women during pregnancy and lactation.
  18. Any other investigator believes that the subject is not suitable for the study, such as the subject has potential compliance issues, cannot complete all tests and assessments according to the protocol requirements.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:其他
  • 分配:随机化
  • 介入模型:顺序分配
  • 屏蔽:双倍的

武器和干预

参与者组/臂
干预/治疗
有源比较器:JS002
JS002, Subcutaneous or intravenous injection
JS002, Subcutaneous or intravenous injection of a single dose of JS002, dose cohort according to ascending dose design
其他名称:
  • Recombinant humanized Anti- PCSK9 monoclonal antibody
安慰剂比较:Placebo,
Placebo,Subcutaneous or intravenous injection
Placebo,Subcutaneous or intravenous injection of a single dose of placebo, dose cohort according to ascending dose design
其他名称:
  • Placebo of Recombinant humanized Anti- PCSK9 monoclonal antibody

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Number of participants with adverse events(SAE, drug-related (S)AE etc)based on physical examinations, vital signs, 12 lead ECGs , laboratory tests and injection site reactions.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration

次要结果测量

结果测量
大体时间
Number of participants with anti-drug antibodies.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration
Serum concentrations of JS002 at different timepoint after the drug administration.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration
Change from baseline in LDL-C and other lipid parameters (TC, HDL-C, non-HDL-C, VLDL-C, ApoB, ApoA1, Lp(a) and TG).
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration

其他结果措施

结果测量
大体时间
Changes over time of serum concentrations of JS002.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration
Changes over time of LDL-C.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration
Change over time of unbound/total serum PCSK9.
大体时间:Up to 84 days after dose administration
Up to 84 days after dose administration

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2017年12月11日

初级完成 (实际的)

2018年8月14日

研究完成 (实际的)

2018年8月14日

研究注册日期

首次提交

2019年12月1日

首先提交符合 QC 标准的

2019年12月11日

首次发布 (实际的)

2019年12月13日

研究记录更新

最后更新发布 (实际的)

2019年12月13日

上次提交的符合 QC 标准的更新

2019年12月11日

最后验证

2019年12月1日

更多信息

与本研究相关的术语

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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