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

Primary Purpose

Mucopolysaccharidosis I

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AGT-181 (HIRMAb-IDUA)

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis I focused on measuring MPS I

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Children's Hospital Oakland
Children's Hospital of Orange County
Emory Healthcare
Ann & Robert H. Lurie Children's Hospital of Chicago
Children's Hospital of Pittsburgh of UPMC
University of Utah Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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

3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

Outcomes

Primary Outcome Measures

Number of participants with adverse events as a measure of safety and tolerability

Secondary Outcome Measures

plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-181)

change in urinary or plasma glycosaminoglycans (GAGs)

change in liver size

change in spleen size

change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid

Full Information

NCT ID

NCT02371226

First Posted

February 19, 2015

Last Updated

February 19, 2023

Sponsor

ArmaGen, Inc

1. Study Identification

Unique Protocol Identification Number

NCT02371226

Brief Title

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

July 2015 (Actual)

Primary Completion Date

January 23, 2017 (Actual)

Study Completion Date

February 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ArmaGen, Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucopolysaccharidosis I

Keywords

MPS I

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Masking Description

Open Label

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

3 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

6-9 mg/kg AGT-181 (HIRMAb-IDUA) administered once weekly x 8 weeks

Intervention Type

Drug

Intervention Name(s)

AGT-181 (HIRMAb-IDUA)

Other Intervention Name(s)

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

Intervention Description

intravenous infusion over 3-4 hours

Primary Outcome Measure Information:

Title

Number of participants with adverse events as a measure of safety and tolerability

Time Frame

eight weeks

Secondary Outcome Measure Information:

Title

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

Title

change in urinary or plasma glycosaminoglycans (GAGs)

Time Frame

8 weeks

Title

change in liver size

Time Frame

8 weeks

Title

change in spleen size

Time Frame

8 weeks

Title

change in levels of heparan sulfate and dermatan sulfate in the cerebrospinal fluid

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrice Rioux, MD PhD

Organizational Affiliation

ArmaGen, Inc

Official's Role

Study Director

Facility Information:

Facility Name

Children's Hospital Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

Children's Hospital of Orange County

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Emory Healthcare

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30033

Country

United States

Facility Name

Ann & Robert H. Lurie Children's Hospital of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Children's Hospital of Pittsburgh of UPMC

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

University of Utah Hospital

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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