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

Tracking Information

• First Submitted Date: October 2, 2014
• First Posted Date: October 13, 2014
• Last Update Posted Date: September 18, 2018
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: March 27, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: Safety and Dose Ranging Study of Insulin Receptor MoAb-IDS Fusion Protein in Patients With Hunter Syndrome
• 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)
• 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: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Treatment

• Condition: Mucopolysaccharidosis II

Intervention

Drug: AGT-182

Recombinant HIRMAb-IDS

Study Arms

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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 16, 2018): 6
• Original Estimated Enrollment (submitted: October 10, 2014): 22
• Actual Study Completion Date: March 27, 2017
• Actual Primary Completion Date: March 27, 2017 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Philippines, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02262338
• Other Study ID Numbers: AGT-182-101
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: ArmaGen, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: ArmaGen, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: ArmaGen, Inc
• Verification Date: September 2018