A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Iduronate 2-Sulfatase (IDS) Fusion Protein, AGT-182 in Adult Patients With Mucopolysaccharidosis II (MPS II, Hunter Syndrome)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- ArmaGen, Inc
- 入组人数
- 6
- 试验地点
- 5
- 主要终点
- number of participants with adverse events as a measure of safety and tolerability
研究概览
简要总结
AGT-182 is a fusion protein containing idursulfase that is intended to deliver the enzyme peripherally and to the brain, when administered intravenously. This study is a safety and dose ranging study to obtain safety and exposure data, as well as information on the biological activity of the investigational drug.
详细描述
This is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter syndrome. Two dose levels, assuming tolerability, are planned sequentially, with safety data from the previous cohort being reviewed prior to escalation to the next higher dose cohort. Subjects will receive weekly doses of AGT-182 for 8 weeks if ERT-naive or agreeing to a 6-week ERT washout, or for 13 weeks if currently taking ERT and not agreeing to washout.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male age 18 years or older
- •Diagnosis of Hunter Syndrome (documented fibroblast or leukocyte IDS enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory - or any level of enzyme deficiency together with the presence of a pathogenic mutation in the IDS gene - and documentation of normal enzymatic activity of at least 1 other sulfatase.)
- •Must fall into one of the following groups:
- •currently receiving standard enzyme replacement therapy (ERT) and be willing to discontinue it for the study duration, taking AGT-182 instead
- •have not received standard ERT for at least 3 months and have elevated uGAGs of at least 3.5 fold above age-related normals at study screening
- •have never received ERT
- •Voluntary written consent
- •Sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
排除标准
- •Refusal to complete screening/baseline evaluations
- •Receipt of an investigational drug within the prior 90 days
- •Any medical condition or other circumstances that may significantly interfere with study compliance
- •Clinically significant spinal cord compression, evidence of cervical instability
- •Known hypersensitivity to idursulfase or any of the components of AGT-182
- •Known to be nonresponsive to standard ERT treatment (i.e., high uGAG values despite taking full dose standard ERT)
- •History of diabetes mellitus or hypoglycemia
- •Contraindication to lumbar puncture, if the patient agrees to this optional assessment
研究组 & 干预措施
Treated subjects
AGT-182 solution for infusion will be administered intravenously at doses of 1.0 mg/kg or 3.0 mg/kg weekly for 8-13 weeks.
干预措施: AGT-182 (Drug)
结局指标
主要结局
number of participants with adverse events as a measure of safety and tolerability
时间窗: 8 weeks (ERT-naive) or 13 weeks (ERT)
次要结局
- change in urinary or plasma glycosaminoglycans (GAGs)(8 weeks (ERT-naive) or 13 weeks (ERT))
- plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)(8 weeks (ERT-naive) or 13 weeks (ERT))
- change in liver or spleen size(8 weeks (ERT-naive) or 13 weeks (ERT))
- change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)(8 weeks (ERT-naive) or 13 weeks (ERT))