A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Adult Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- ArmaGen, Inc
- 入组人数
- 3
- 试验地点
- 6
- 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-181 is a fusion protein containing alpha-L-Iduronidase 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Male age 18 years or older
- •Diagnosis of MPS I (documented fibroblast or leukocyte IDUA enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory)
- •Voluntary written consent by patient or legally responsible representative
- •All women of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
- •Negative pregnancy test (females)
- •Must not have received ERT for at least 6 weeks prior to AGT-181 treatment
- •Must have elevated urinary GAGs if no ERT has been received in the prior 3 months
排除标准
- •Refusal to complete baseline evaluations.
- •Any medical condition or other circumstances that may significantly interfere with study compliance
- •Receipt of an investigational drug within the prior 90 days
- •History of diabetes mellitus or hypoglycemia
- •Clinically significant spinal cord compression, evidence of cervical instability.
- •Known hypersensitivity to alpha-L-iduronidase or any of the components of AGT-
- •Known to be nonresponsive to standard ERT treatment.
- •Previously successful (engrafted) hematopoietic stem cell transplantation that resulted in normalization of urinary GAGs.
- •Contraindication for lumbar puncture
研究组 & 干预措施
Cohort 1
1 mg/kg AGT-181 (fusion protein of anti-human insulin receptor monoclonal antibody and alpha-L-iduronidase; HIRMAb-IDUA) administered once weekly x 8 weeks
干预措施: AGT-181 (HIRMAb-IDUA) (Drug)
Cohort 2
3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks
干预措施: AGT-181 (HIRMAb-IDUA) (Drug)
Cohort 3
6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks
干预措施: AGT-181 (HIRMAb-IDUA) (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: eight weeks
次要结局
- plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)(8 weeks)
- change in urinary or plasma glycosaminoglycans (GAGs)(8 weeks)
- change in liver size(8 weeks)
- change in spleen size(8 weeks)
- change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid(8 weeks)