Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02371226
Recruitment Status : Unknown
Verified March 2017 by ArmaGen, Inc.
Recruitment status was:  Active, not recruiting
First Posted : February 25, 2015
Last Update Posted : March 6, 2017
Sponsor:
Information provided by (Responsible Party):
ArmaGen, Inc

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis I Drug: AGT-181 (HIRMAb-IDUA) Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
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)
Actual Study Start Date : July 2015
Actual Primary Completion Date : February 2017
Estimated Study Completion Date : June 2017


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 Name: 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 Name: 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 Name: fusion protein of monoclonal antibody to human insulin receptor fused to alpha-L-iduronidase




Primary Outcome Measures :
  1. Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: eight weeks ]

Secondary Outcome Measures :
  1. plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181) [ Time Frame: 8 weeks ]
  2. change in urinary or plasma glycosaminoglycans (GAGs) [ Time Frame: 8 weeks ]
  3. change in liver size [ Time Frame: 8 weeks ]
  4. change in spleen size [ Time Frame: 8 weeks ]
  5. change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid [ Time Frame: 8 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02371226


Locations
Layout table for location information
United States, California
Children's Hospital Oakland
Oakland, California, United States, 94609
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Georgia
Emory Healthcare
Decatur, Georgia, United States, 30033
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
ArmaGen, Inc
Investigators
Layout table for investigator information
Study Director: Patrice Rioux, MD PhD ArmaGen, Inc
Layout table for additonal information
Responsible Party: ArmaGen, Inc
ClinicalTrials.gov Identifier: NCT02371226    
Other Study ID Numbers: AGT-181-102
First Posted: February 25, 2015    Key Record Dates
Last Update Posted: March 6, 2017
Last Verified: March 2017
Keywords provided by ArmaGen, Inc:
MPS I
Additional relevant MeSH terms:
Layout table for MeSH terms
Mucopolysaccharidoses
Mucopolysaccharidosis I
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs