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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Mucopolys

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 Summary: 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.
Sponsor: ArmaGen, Inc

Current Primary Outcome: 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:

  • 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:

  • 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:

  • 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 ]


Information By: ArmaGen, Inc

Dates:
Date Received: October 2, 2014
Date Started: April 2015
Date Completion: October 2017
Last Updated: February 28, 2017
Last Verified: February 2017