A Study to Evaluate the Safety and Pharmacology of Subcutaneous Administration of CINRYZE With Recombinant Human Hyaluronidase

Study Overview
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Brief Summary
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The objectives of the study are to: Evaluate the safety and tolerability of subcutaneously administered CINRYZE with recombinant human hyaluronidase (rHuPH20) in subjects with hereditary angioedema (HAE) who previously participated in CINRYZE Study 0624-200 (NCT01095497) Characterize the pharmacokinetics and pharmacodynamics of subcutaneously administered CINRYZE with rHuPH20 Assess the immunogenicity of CINRYZE following subcutaneous (SC) administration of CINRYZE with rHuPH20

Official Title
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An Open-label Multiple-dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Hereditary Angioedema

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: CINRYZE with rHuPH20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for this protocol, a subject must: Provide informed consent/assent, as appropriate. Have previously participated in CINRYZE Study 0624-200 and completed the subcutaneous therapy period in that study. During the 3 consecutive months prior to screening, have a history of less than 1 HAE attack per month (average) that required treatment with C1 INH therapy or other blood products. Agree to avoid his/her known HAE triggers during the study to the best of his/her ability. Exclusion Criteria: To be eligible for this protocol, a subject must not: Have received C1 INH therapy or any blood products for treatment or prevention of an HAE attack within 14 days prior to the first dose of study drug. Have received any ecallantide (Kalbitor), icatibant (Firazyr), or antifibrinolytics (e.g., tranexamic acid) within 14 days prior to the first dose of study drug. Have any change (start, stop, or change in dose) in androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 14 days prior to the first dose of study drug. If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug. Have a history of abnormal blood clotting. Have a history of allergic reaction to products containing C1 INH or other blood products. Have a known allergy to hyaluronidase or any other ingredient in rHuPH20. Be pregnant or breastfeeding. Have received an investigational study drug within 30 days prior to the first dose of study drug.

Ages Eligible for Study
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Minimum Age: 12 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC CINRYZE with rHuPH20 Dose Level 1<br>Subcutaneous injection of 1000 Units of CINRYZE with 20,000 Units of rHuPH20 twice weekly for two weeks | Biological: CINRYZE with rHuPH20<br> <br> * Other names: Recombinant human hyaluronidase;|
| Experimental: SC CINRYZE with rHuPH20 Dose Level 2<br>Subcutaneous injection of 2000 Units of CINRYZE with 40,000 Units of rHuPH20 twice weekly for two weeks | Biological: CINRYZE with rHuPH20<br> <br> * Other names: Recombinant human hyaluronidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events, Number of Participants With Local Injection Site Reactions, and Number of Participants Who Discontinue Study Drug or Withdraw From the Study |  | 18 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change C1 Inhibitor (C1INH) | Mean Change in Baseline in Observed Plasma Concentration of C1 Inhibitor (C1INH) Antigen. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration. | 18 days | 
| Mean Change C4 Compliment | Mean Change in Baseline in Observed Plasma Concentration of C4 Compliment. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration. | 18 days | 
| Number of Subjects With C1 INH Antibodies |  | Day 1 (pre-dose), Day 18 (168 h post Dose 4), and 30 (±2) days after the last dose of study drug (Dose 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE, C1 esterase inhibitor, C1 INH, Subcutaneous, hyaluronidase, rHuPH20