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

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)

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.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis II
• Intervention / Treatment: Drug: AGT-182

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany
    • ZKJM MC University of Mainz
• Philippines
  • Manila, Philippines
    • Institute of Human Genetics, National Inst of Health, University of the Philippines
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: ArmaGen, Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2015
• Primary Completion (ACTUAL): March 27, 2017
• Study Completion (ACTUAL): March 27, 2017

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (ESTIMATE): October 13, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 16, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Hunter Syndrome; MPS II
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidosis II; Mucopolysaccharidoses
• Other Study ID Numbers: AGT-182-101