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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by ArmaGen, Inc
Sponsor:
Information provided by (Responsible Party):
ArmaGen, Inc
ClinicalTrials.gov Identifier:
NCT02262338
First received: October 2, 2014
Last updated: February 28, 2017
Last verified: February 2017
  Purpose
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 Intervention Phase
Mucopolysaccharidosis II
Drug: AGT-182
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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)

Resource links provided by NLM:


Further study details as provided by ArmaGen, Inc:

Primary Outcome Measures:
  • 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:
  • 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) ]
  • change in urinary or plasma glycosaminoglycans (GAGs) [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
  • change in liver or spleen size [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
  • change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs) [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]

Estimated Enrollment: 8
Actual Study Start Date: April 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02262338

Contacts
Contact: Terry Bevirt +1 818-436-0222 tbevirt@armagen.com

Locations
United States, California
Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
Contact: Jacqueline Madden, PNP    510-428-3885 ext 5745    jmadden@mail.cho.org   
Contact: JoAnn Johnson, MPH, CCRC    510-428-3885 ext 5421    jajohnson@mail.cho.org   
Principal Investigator: Paul Harmatz, MD         
Children's Hospital of Orange County Completed
Orange, California, United States, 92868
United States, Georgia
Emory University Completed
Decatur, Georgia, United States, 30033
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Withdrawn
Chicago, Illinois, United States, 60611
United States, Minnesota
University of Minnesota Withdrawn
Minneapolis, Minnesota, United States, 55117
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Withdrawn
Pittsburgh, Pennsylvania, United States, 15224
United States, Utah
University of Utah Hospital Withdrawn
Salt Lake City, Utah, United States, 84132
United States, Virginia
O & O Alpan, LLC Withdrawn
Fairfax, Virginia, United States, 22030
Germany
ZKJM MC University of Mainz Not yet recruiting
Mainz, Germany
Contact: Julia Hennermann, MD    +49(0) 6131 175754    julia.hennermann@unimedizin-mainz.de   
Contact: Petra Kleinhans    +49 (0) 6131-174579    Petra.Kleinhans@unimedizin-mainz.de   
Principal Investigator: Julia Hennermann, MD         
Netherlands
Erasmus Medical Center Withdrawn
Rotterdam, Netherlands
Philippines
Institute of Human Genetics, National Inst of Health, University of the Philippines Completed
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     History of Changes
Other Study ID Numbers: AGT-182-101
Study First Received: October 2, 2014
Last Updated: February 28, 2017

Keywords provided by ArmaGen, Inc:
MPS II
Hunter Syndrome

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis II
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

ClinicalTrials.gov processed this record on May 25, 2017