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

• ClinicalTrials.gov Identifier: NCT02262338
• Recruitment Status: Completed
• First Posted: October 13, 2014
• Last Update Posted: September 18, 2018
• Sponsor: ArmaGen, Inc
• Information provided by (Responsible Party): ArmaGen, Inc

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.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis II	Drug: AGT-182	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: March 27, 2017
• Actual Study Completion Date: March 27, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treated subjects; 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; Recombinant HIRMAb-IDS

Outcome Measures

Primary Outcome Measures :

1. number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]

Secondary Outcome Measures :

1. plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182) [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
2. change in urinary or plasma glycosaminoglycans (GAGs) [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
3. change in liver or spleen size [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
4. change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs) [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Children's Hospital Oakland

Oakland, California, United States, 94609

Children's Hospital of Orange County

Orange, California, United States, 92868

United States, Georgia

Emory University

Decatur, Georgia, United States, 30033

Germany

ZKJM MC University of Mainz

Mainz, Germany

Philippines

Institute of Human Genetics, National Inst of Health, University of the Philippines

Manila, Philippines

Sponsors and Collaborators

ArmaGen, Inc

Investigators

• Study Director: Patrice Rioux, MD PhD; ArmaGen, Inc

More Information

• Responsible Party: ArmaGen, Inc
• ClinicalTrials.gov Identifier: NCT02262338
• Other Study ID Numbers: AGT-182-101
• First Posted: October 13, 2014
• Last Update Posted: September 18, 2018
• Last Verified: September 2018

Keywords provided by ArmaGen, Inc:

MPS II; Hunter Syndrome

Additional relevant MeSH terms:

Mucopolysaccharidosis II; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System