Safety and Dose Ranging Study of Insulin Receptor MAb-IDUA Fusion Protein in Patients With MPS I

Mucopolysaccharidosis I Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02371226
• Other study ID #: AGT-181-102
• Status: Completed
• Phase: Phase 1
• Start date: July 2015
• Est. completion date: February 1, 2017

Study information

• Verified date: February 2023
• Source: ArmaGen, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: February 1, 2017
• Est. primary completion date: January 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis I

Intervention

Drug:
• AGT-181 (HIRMAb-IDUA)
intravenous infusion over 3-4 hours

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Emory Healthcare	Decatur	Georgia
United States	Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	University of Utah Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
ArmaGen, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events as a measure of safety and tolerability		eight weeks
Secondary	plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)		8 weeks
Secondary	change in urinary or plasma glycosaminoglycans (GAGs)		8 weeks
Secondary	change in liver size		8 weeks
Secondary	change in spleen size		8 weeks
Secondary	change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid		8 weeks