Safety and Dose Ranging Study of Insulin Receptor MAb-IDUA Fusion Protein in Patients With MPS I
Phase 1
Completed
- Conditions
- Mucopolysaccharidosis I
- Interventions
- Drug: AGT-181 (HIRMAb-IDUA)
- Registration Number
- NCT02371226
- Lead Sponsor
- ArmaGen, Inc
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3
Inclusion Criteria
- 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
Exclusion Criteria
- 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-181.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 3 AGT-181 (HIRMAb-IDUA) 6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks Cohort 1 AGT-181 (HIRMAb-IDUA) 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 Cohort 2 AGT-181 (HIRMAb-IDUA) 3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks
- Primary Outcome Measures
Name Time Method Number of participants with adverse events as a measure of safety and tolerability eight weeks
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (6)
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital Oakland
🇺🇸Oakland, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Emory Healthcare
🇺🇸Decatur, Georgia, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States