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

Mucopolysaccharidosis II Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02262338
• Other study ID #: AGT-182-101
• Status: Completed
• Phase: Phase 1
• Start date: April 2015
• Est. completion date: March 27, 2017

Study information

• Verified date: September 2018
• Source: ArmaGen, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 27, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Drug:
• AGT-182
Recombinant HIRMAb-IDS

Locations

Country	Name	City	State
Germany	ZKJM MC University of Mainz	Mainz
Philippines	Institute of Human Genetics, National Inst of Health, University of the Philippines	Manila
United States	Emory University	Decatur	Georgia
United States	Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
ArmaGen, Inc

Countries where clinical trial is conducted

United States,  Germany,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of participants with adverse events as a measure of safety and tolerability		8 weeks (ERT-naive) or 13 weeks (ERT)
Secondary	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)
Secondary	change in urinary or plasma glycosaminoglycans (GAGs)		8 weeks (ERT-naive) or 13 weeks (ERT)
Secondary	change in liver or spleen size		8 weeks (ERT-naive) or 13 weeks (ERT)
Secondary	change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)		8 weeks (ERT-naive) or 13 weeks (ERT)