Extension Study Evaluating Long Term Safety and Activity of AGT-181 in Children With MPS I

Study Overview
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Brief Summary
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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 is a long term safety and tolerability study of AGT-181 in patients with MPS I who completed the previous 26-week study, AGT-181-101. Information on the biological activity of the investigational drug will also be collected.

Detailed Description
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AGT-181-101E is a safety and tolerability study of AGT-181 in patients with MPS I who completed the previous 26-week study, AGT-181-101. Information on the biological activity of the investigational drug will be collected as well as longitudinal safety information.

Official Title
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An Extension Study Evaluating Long Term Safety and Activity of AGT-181 in Patients With Mucopolysaccharidosis I Who Were Previously Enrolled in Studies With AGT-181

Conditions
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Mucopolysaccharidosis I

Intervention / Treatment
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* Drug: AGT-181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2 years of age or older (and less than 18) Must have been previously enrolled in study AGT-181-101 Written consent and assent as required Female patients must not be pregnant, willing to utilize appropriate birth control methods and undergo pregnancy testing during the study Exclusion Criteria: Refusal to complete all assessments Pregnant or Lactating Received investigational drug within 1 year prior to study enrollment Medical condition or extenuating circumstance that, in the opinion of the investigator, may interfere with study compliance Clinically significant spinal cord compression or evidence of cervical instability (i.e. expected to require intervention during study participation) Has developed clinically relevant hypersensitivity/anaphylactoid reactions to AGT-181

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will be assigned to 1.0, 3.0 or 6.0 mg/kg (same dose taken during the previous study, AGT-181-101)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGT-181<br>Human Insulin Receptor Monoclonal Antibody-Human alpha-L-iduronidase (HIRMAb-IDUA) fusion protein | Drug: AGT-181<br>* Human Insulin Receptor Monoclonal Antibody-Human alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with adverse events as a measure of safety and tolerability | Incidence and prevalence of adverse events | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total urinary glycosaminoglycans (GAGs) | Change in total urinary glycosaminoglycans (GAGs) | 24 months | 
| Urinary heparan sulfate and dermatan sulfate | Change in urinary heparan sulfate and dermatan sulfate | 24 months | 
| Plasma heparan sulfate and dermatan sulfate | Change in plasma heparan sulfate and dermatan sulfate | 24 months | 
| CSF heparan sulfate and dermatan sulfate | Change in CSF heparan sulfate and dermatan sulfate | 24 months | 
| liver and/or spleen volume | Change in liver and/or spleen volume measured by MRI | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS I; Hurler Syndrome