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

Primary Purpose

Mucopolysaccharidosis II

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AGT-182

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis II focused on measuring MPS II, Hunter Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Children's Hospital Oakland
Children's Hospital of Orange County
Emory University
ZKJM MC University of Mainz
Institute of Human Genetics, National Inst of Health, University of the Philippines

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treated subjects

Arm Description

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.

Outcomes

Primary Outcome Measures

number of participants with adverse events as a measure of safety and tolerability

Secondary Outcome Measures

plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)

change in urinary or plasma glycosaminoglycans (GAGs)

change in liver or spleen size

change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)

Full Information

NCT ID

NCT02262338

First Posted

October 2, 2014

Last Updated

September 16, 2018

Sponsor

ArmaGen, Inc

1. Study Identification

Unique Protocol Identification Number

NCT02262338

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

April 2015 (Actual)

Primary Completion Date

March 27, 2017 (Actual)

Study Completion Date

March 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ArmaGen, Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucopolysaccharidosis II

Keywords

MPS II, Hunter Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Masking Description

Open Label

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treated subjects

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

AGT-182

Intervention Description

Recombinant HIRMAb-IDS

Primary Outcome Measure Information:

Title

number of participants with adverse events as a measure of safety and tolerability

Time Frame