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

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)

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.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I
• Intervention / Treatment: Drug: AGT-181 (HIRMAb-IDUA)

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 1 mg/kg AGT-181 (fusion protein of anti-human insulin receptor monoclonal antibody and alpha-L-iduronidase; HIRMAb-IDUA) administered once weekly x 8 weeks	Drug: AGT-181 (HIRMAb-IDUA); intravenous infusion over 3-4 hours; Other Names: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase
Experimental: Cohort 2; 3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks	Drug: AGT-181 (HIRMAb-IDUA); intravenous infusion over 3-4 hours; Other Names: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase
Experimental: Cohort 3; 6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks	Drug: AGT-181 (HIRMAb-IDUA); intravenous infusion over 3-4 hours; Other Names: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	eight weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)	8 weeks
change in urinary or plasma glycosaminoglycans (GAGs)	8 weeks
change in liver size	8 weeks
change in spleen size	8 weeks
change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid	8 weeks

Collaborators and Investigators

• Sponsor: ArmaGen, Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): January 23, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: MPS I
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: AGT-181-102