Study of Idursulfase-beta (GC1111) in Hunter Syndrome

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of three doses of GC1111 in patients with Hunter Syndrome. Participants will be randomized to one of three doses of GC1111 or comparator.

Detailed Description
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This is a randomized, double-blind, active-controlled, dose-ranging study, where patient will receive one of the three doses of GC1111 (0.5 mg/kg, 1.0 mg/kg, and 1.5 mg/kg) or ELAPRASE 0.5 mg/kg. Approximately 20 patients will be administrated each study drug once every week as an iv infusion for 24 weeks. Efficacy of GC1111 will be evaluated in Six-Minute Walk Test (6MWT), urine Glycosaminoglycans(uGAG), liver and spleen volume, percent predicted Forced Vital Capacity(FVC), and cardiac size and function. Also immunogenicity, Pharmacokinetics(PK) and safety will be evaluated.

Official Title
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Phase 2, Randomized, Double-blind, Active-controlled, Dose-ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Idursulfase-beta (GC1111) in Hunter Syndrome (Mucopolysaccharidosis II) Patients

Conditions
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Mucopolysaccharidosis II

Intervention / Treatment
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* Biological: idursulfase beta
* Biological: idursulfase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients between 5 and 35 years of age Informed consent form signed Patients diagnosed with hunter syndrome Previously untreated with an enzyme replacement therapy Exclusion Criteria: History of tracheostomy, bone marrow transplant, or cord blood transplant Treatment with another investigational product within 30 days prior to the start of study drug Known hypersensitivity of any of the ingredients of study drug Patient with severe hunter syndrome who cannot perform 6MWT Female patients

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>0.5 mg/kg, iv, weekly infusion of idursulfase beta for 24 weeks | Biological: idursulfase beta<br>* IV, weekly infusion for 24 weeks<br>* Other names: GC1111;|
| Experimental: Arm 2<br>1.0 mg/kg, iv, weekly infusion of idursulfase beta for 24 weeks | Biological: idursulfase beta<br>* IV, weekly infusion for 24 weeks<br>* Other names: GC1111;|
| Experimental: Arm 3<br>1.5 mg/kg, iv, weekly infusion of idursulfase beta for 24 weeks | Biological: idursulfase beta<br>* IV, weekly infusion for 24 weeks<br>* Other names: GC1111;|
| Active Comparator: Arm 4<br>0.5mg/kg, iv, weekly infusion of idursulfase for 24 weeks | Biological: idursulfase<br>* 0.5 mg/kg, iv, weekly infusion for 24 weeks<br>* Other names: Elaprase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in urinary GAG(Glycosaminoglycans) at Week 25 |  | Baseline to Week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary GAG at Week 25 |  | Baseline to Week 25 | 
| Change from baseline in Six Minute Walk Test at Week 25 |  | Baseline to Week 25 | 
| Percent change from baseline in Six Minute Walk Test at Week 25 |  | Baseline to Week 25 | 
| Change from baseline in Liver volume at Week 25 | Liver volume measured by MRI | Baseline to Week 25 | 
| Percent change from baseline in Liver volume at Week 25 | Liver volume measured by MRI | Baseline to Week 25 | 
| Change from baseline in Spleen volume at Week 25 | Spleen volume measured by MRI | Baseline to Week 25 | 
| Percent change from baseline in Spleen volume at Week 25 | Spleen volume measured by MRI | Baseline to Week 25 | 
| Incidence of Adverse Events and Serious Adverse Events |  | Baseline to Week 25 | 
| Safety changes from baseline in clinical laboratory tests, physical examination and vital signs |  | Baseline to Week 25 | 
| Immunogenicity | anti-drug-antibody | Baseline to Week 25 | 
| Pharmacokinetic profile - Area under the serum concentration time curve (AUClast) |  | 1 and 17 week | 
| Pharmacokinetic profile - Maximum observed peak plasma concentration (Cmax) |  | 1 and 17 week | 
| Pharmacokinetic profile - Time at which Cmax is observed (Tmax) |  | 1 and 17 week |