A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CINRYZE Administration

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 CINRYZE administered by subcutaneous injection in subjects with hereditary angioedema Characterize the pharmacokinetics and pharmacodynamics of CINRYZE administered by subcutaneous injection Assess the immunogenicity of CINRYZE following subcutaneous administration

Official Title
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An Open-Label Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous (SC) Versus Intravenous (IV) Administration of CINRYZE in Adolescents and Adults With Hereditary Angioedema (HAE)

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: CINRYZE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for this protocol, a subject must: Have a confirmed diagnosis of HAE. During the 3 consecutive months prior to screening, have a history of less than 1 HAE attack per month (average) treated with C1INH therapy or any other blood products, ecallantide (Kalbitor), icatibant (Firazyr), antifibrinolytics (e.g., tranexamic acid), IV fluids, or narcotic analgesics. Agree to strictly adhere to the protocol-defined schedule of assessments and procedures. Exclusion Criteria: To be eligible for this protocol, a subject must not: Have received C1INH therapy or any blood products for treatment or prevention of an HAE attack within 14 days prior to the first dose. Have received any ecallantide (Kalbitor), icatibant (Firazyr), or antifibrinolytics (e.g., tranexamic acid) within 14 days prior to the first dose. 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. 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. Have a history of abnormal blood clotting or other coagulopathy. Have a history of allergic reaction to CINRYZE or other blood products. Be pregnant or breastfeeding. Have received an immunization within 30 days prior to the first dose. Have participated in any other investigational drug study within 30 days prior to the first dose.

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV CINRYZE First, Then SC CINRYZE Dose 1<br> | Biological: CINRYZE<br>* C1 esterase inhibitor (human)<br>|
| Experimental: IV CINRYZE First, Then SC CINRYZE Dose 2<br> | Biological: CINRYZE<br>* C1 esterase inhibitor (human)<br>|

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 Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study. |  | 18 days in each treatment period | 

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 in each treatment period | 
| 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 in each treatment period | 
| Number of Participants With C1 Inhibitor (INH) Antibodies |  | 18 days in each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous, HAE, C1 inhibitor (C1INH)