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

Phase 2

Completed

Brief Summary: The objectives of the study are to:

1. 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)

2. Characterize the pharmacokinetics and pharmacodynamics of subcutaneously administered CINRYZE with rHuPH20

3. Assess the immunogenicity of CINRYZE following subcutaneous (SC) administration of CINRYZE with rHuPH20

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
SC CINRYZE with rHuPH20 Dose Level 2	CINRYZE with rHuPH20	Subcutaneous injection of 2000 Units of CINRYZE with 40,000 Units of rHuPH20 twice weekly for two weeks
SC CINRYZE with rHuPH20 Dose Level 1	CINRYZE with rHuPH20	Subcutaneous injection of 1000 Units of CINRYZE with 20,000 Units of rHuPH20 twice weekly for two weeks

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)
Mean Change C1 Inhibitor (C1INH)	18 days	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.
Mean Change C4 Compliment	18 days	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.