Clinical trial NCT02262338: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mucopolysaccharidosis II
Keywords: MPS II
Hunter Syndrome
Lead sponsor: ArmaGen, Inc
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: number of participants with adverse events as a measure of safety and tolerability
timeFrame: 8 weeks (ERT-naive) or 13 weeks (ERT)
Secondary outcomes:
measure: plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)
timeFrame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in urinary or plasma glycosaminoglycans (GAGs)
timeFrame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in liver or spleen size
timeFrame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)
timeFrame: 8 weeks (ERT-naive) or 13 weeks (ERT)
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Decatur
country: United States
facility: Emory University
state: Georgia
city: Mainz
country: Germany
facility: ZKJM MC University of Mainz
city: Manila
country: Philippines
facility: Institute of Human Genetics, National Inst of Health, University of the Philippines
Study officials:
affiliation: ArmaGen, Inc
name: Patrice Rioux, MD PhD
role: STUDY_DIRECTOR
References: