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

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

Tracking Information
First Submitted Date  ICMJE October 2, 2014
First Posted Date  ICMJE October 13, 2014
Last Update Posted Date September 18, 2018
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date March 27, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 8 weeks (ERT-naive) or 13 weeks (ERT) ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability, Stage 1 [ Time Frame: four weeks ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability, Stage 2 [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182, Stage 1 [ Time Frame: 4 weeks ]
    pharmacokinetic parameters will be estimated based on plasma antigen concentration
  • plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182, Stage 2 [ Time Frame: 6 months ]
    pharmacokinetic parameters will be estimated based on plasma antigen concentration
  • change in urinary or plasma glycosaminoglycans (GAGs), Stage 1 [ Time Frame: 4 weeks ]
  • change in urinary or plasma glycosaminoglycans (GAGs), Stage 2 [ Time Frame: 6 months ]
  • change in liver size, Stage 1 [ Time Frame: 4 weeks ]
    by palpation
  • change in liver size, Stage 2 [ Time Frame: 6 months ]
    by abdominal MRI
  • ability to perform activities of daily living, Stage 1 [ Time Frame: 4 weeks ]
    as reported by patient/parent
  • patient well being, Stage 2 [ Time Frame: 6 months ]
    assessed by age-appropriate quality of life scales (Infant and Toddler Quality of LIfe Questionnaire or Child Health Questionnaire)
  • changes in lung function capacity [ Time Frame: 6 months ]
  • changes in range of motion [ Time Frame: 6 months ]
  • changes in left ventricular mass/hypertrophy [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 10, 2014)
  • change in CNS by imaging [ Time Frame: 6 months ]
  • change in cerebral spinal fluid GAGs [ Time Frame: 6 months ]
  • change in neurocognitive function [ Time Frame: 6 months ]
    based on scores from age appropriate neurocognitive tests, including Vineland Adaptive Behavior Scales, Bayley Scales of Infant and Toddler Development and/or Kaufman Assessment Battery for Children
 
Descriptive Information
Brief Title  ICMJE Safety and Dose Ranging Study of Insulin Receptor MoAb-IDS Fusion Protein in Patients With Hunter Syndrome
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE Mucopolysaccharidosis II
Intervention  ICMJE Drug: AGT-182
Recombinant HIRMAb-IDS
Study Arms  ICMJE 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.
Intervention: Drug: AGT-182
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 16, 2018)
6
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2014)
22
Actual Study Completion Date  ICMJE March 27, 2017
Actual Primary Completion Date March 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Philippines,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02262338
Other Study ID Numbers  ICMJE AGT-182-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ArmaGen, Inc
Study Sponsor  ICMJE ArmaGen, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Patrice Rioux, MD PhD ArmaGen, Inc
PRS Account ArmaGen, Inc
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP