Safety and Dose Ranging Study of Insulin Receptor MoAb-IDS Fusion Protein in Patients With Hunter Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Mucopolysaccharidosis II

Intervention / Treatment
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* Drug: AGT-182


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated subjects<br>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. | Drug: AGT-182<br>* Recombinant HIRMAb-IDS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants with adverse events as a measure of safety and tolerability |  | 8 weeks (ERT-naive) or 13 weeks (ERT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 urinary or plasma glycosaminoglycans (GAGs) |  | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS II, Hunter Syndrome