A Study of the Safety and Immunogenicity of Repeated rhC1INH Administration

Study Overview
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Brief Summary
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Hereditary angioedema (HAE) is a disease characterized by recurrent tissue swelling affecting various body locations. Recent literature shows that patients with frequent attacks may benefit from long-term prophylaxis. This study aims to evaluate the safety and prophylactic effect of weekly administrations of 50 IU/kg recombinant C1 Inhibitor (rhC1INH).

Official Title
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An Open-label Exploratory Phase II Study of the Safety and Immunogenicity of Repeated rhC1INH Administration of 50 U/Kg in Patients With Hereditary C1 Inhibitor Deficiency (HAE)

Conditions
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Genetic Disorders, Hereditary Angioedema

Intervention / Treatment
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* Drug: Recombinant Human C1 Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 18 years Signed informed consent Comfirmed diagnosis of HAE with baseline plasma level of functional C1INH activity of less than 50% of normal, and/or proven HAE ,mutation in C1INH gene. Exclusion Criteria: A history of anaphylaxis or severe allergy (i.e. requiring medication) to food, proteins and/or drugs. A history of allergic reactions to C1INH products or rabbit protein. Any reported SAE related to study drug administration (withdrawal criterium) Elevated IgE against rabbit dander (>0.35 kU/L; ImmunoCap assay; Phadia) A diagnosis of acquired C1INH deficiency. Woman of child bearing potential, pregnancy or breast-feeding previous treatment within the last 3 months with plasma-derived C1INH Any clinically significant abnormality in the routine haematology, biochemistry and urinalysis Any condition or treatment that in the opinion of the investigator might interfere with the evaluation of the study objectives. Any changes since screening that would exclude subject based on above exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Recombinant Human C1 Inhibitor<br>Weekly administration of 50 IU/kg Recombinant Human C1 Inhibitor | Drug: Recombinant Human C1 Inhibitor<br>* 50 IU/kg rhC1INH, IV injection over 4 to 5 minutes, once weekly over an 8-week treatment period.<br>* Other names: Ruconest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAE Attacks/Week | Prior to the treatment period, patients enrolled in the study, were asked about the amount of HAE attacks in the past 2 years, (calculated to attacks/week), this number is defined as Historical. During the treatment period, patients received a dose of 50 IU/kg of rhC1INH administered by slow IV injection over 4 to 5 minutes, once a week during an eight week period. The amount of attacks during this period is defined as Prophylaxis (calculated to attacks/week). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters. | PK/PD parameters will be based on concentration time curves after the 1st and 8th rhC1INH administration.(ratio visit 8/ visit 1, based on the area under the curve from baseline up to 4 hours after administration (AUC 0-4) | 8 weeks |