Clinical trial NCT02371226: Safety and Dose Ranging Study of Insulin Receptor MAb-IDUA Fusion Protein in Patients With MPS I
Official title: A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Adult Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mucopolysaccharidosis I
Keywords: MPS I
Lead sponsor: ArmaGen, Inc
Sponsor class: INDUSTRY
First posted: 2015-02-25
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: AGT-181 is a fusion protein containing alpha-L-Iduronidase 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.


Eligibility criteria: Inclusion Criteria:

* Male age 18 years or older
* Diagnosis of MPS I (documented fibroblast or leukocyte IDUA enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory)
* Voluntary written consent by patient or legally responsible representative
* All women of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
* Negative pregnancy test (females)
* Must not have received ERT for at least 6 weeks prior to AGT-181 treatment
* Must have elevated urinary GAGs if no ERT has been received in the prior 3 months

Exclusion Criteria:

* Refusal to complete baseline evaluations.
* Any medical condition or other circumstances that may significantly interfere with study compliance
* Receipt of an investigational drug within the prior 90 days
* History of diabetes mellitus or hypoglycemia
* Clinically significant spinal cord compression, evidence of cervical instability.
* Known hypersensitivity to alpha-L-iduronidase or any of the components of AGT-181.
* Known to be nonresponsive to standard ERT treatment.
* Previously successful (engrafted) hematopoietic stem cell transplantation that resulted in normalization of urinary GAGs.
* Contraindication for lumbar puncture

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: eight weeks
Secondary outcomes:
measure: plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)
timeFrame: 8 weeks
measure: change in urinary or plasma glycosaminoglycans (GAGs)
timeFrame: 8 weeks
measure: change in liver size
timeFrame: 8 weeks
measure: change in spleen size
timeFrame: 8 weeks
measure: change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid
timeFrame: 8 weeks
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 Healthcare
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
Study officials:
affiliation: ArmaGen, Inc
name: Patrice Rioux, MD PhD
role: STUDY_DIRECTOR
References: