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

ArmaGen

Status and phase: Completed; Phase 1

Conditions: Mucopolysaccharidosis I

Treatments: Drug: AGT-181 (HIRMAb-IDUA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02371226

AGT-181-102

Details and patient eligibility

About

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.

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 participants in 3 patient groups

Cohort 1

Experimental group

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

Treatment:

Drug: AGT-181 (HIRMAb-IDUA)

Cohort 2

Experimental group

Description:

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

Treatment:

Drug: AGT-181 (HIRMAb-IDUA)

Cohort 3

Experimental group

Description:

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

Treatment:

Drug: AGT-181 (HIRMAb-IDUA)