Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

Study Overview
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Brief Summary
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This study is being conducted to confirm the efficacy, safety, and immunogenicity of recombinant human C1 inhibitor (rhC1INH) at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in Hereditary Angioedema (HAE) patients.

Detailed Description
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HAE is characterized by recurrent localized angioedema caused by uncontrolled activation of the complement and contact systems due to a congenital deficiency of functional C1 inhibitor. rhC1INH has been developed to offer a more widely available therapeutic alternative to the existing plasma-derived C1INH (pdC1INH) products that have been used in the treatment of acute angioedema attacks patients with HAE. Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack will be evaluated for eligibility. 75 eligible patients will be randomized (3:2) to receive an intravenous infusion of rhC1INH or saline in a double-blind fashion. Open-label rhC1INH may be provided as rescue medication to patients who do not experience the beginning of relief within 4 hours or who experience life-threatening oropharyngeal-laryngeal angioedema symptoms. Any patient having received a randomized treatment will be allowed to receive treatment with rhC1INH in an open-label fashion for subsequent eligible attacks.

Official Title
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A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks of Angioedema in Patients With HAE

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: rhC1INH
* Drug: Placebo (Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 13 years Signed written informed consent Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal Willingness and ability to comply with all protocol procedures Clinical symptoms of an eligible HAE attack with onset less than 5 hours before the time of initial evaluation Exclusion Criteria: Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit dander IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent). A diagnosis of acquired C1INH deficiency (AAE) Pregnancy, or breastfeeding, or current intention to become pregnant Treatment with any investigational drug in the past 30 days Known or suspected addiction to drug and/or alcohol abuse Suspicion for an alternate explanation of the symptoms other than acute HAE attack

Ages Eligible for Study
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Minimum Age: 13 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhC1INH<br> | Drug: rhC1INH<br>* One i.v. injection of rhC1INH at the dose of 50 U/kg, for patients up to 84 kg; one i.v. injection of rhC1INH at the dose of 4200U (2 vials) for patients of 84 kg body weight or greater.<br>|
| Placebo Comparator: Placebo (Saline)<br> | Drug: Placebo (Saline)<br>* One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Beginning of Relief of Symptoms | Time to beginning of relief is the time lapsed from the beginning of the infusion of study medication to the beginning of a beneficial effect based on patient's responses to the Treatmetn Effect Questionnaire (TEQ) for the primary attack location. The beginning of relief is defined as the first timepoint at which The patient reports any of the following answers for TEQ question 1: A little better, Better or Much better; and; The patient reports the following answer for TEQ question 2: Yes; and, There is persistence in improvement at the next assessment time, i.e.either the same or a better response to Question 1 and Yes to Question 2. | Patients observed for 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Minimal Symptoms | The key secondary efficacy endpoint was the time to minimal symptoms at all locations. The time to achieving minimal symptoms was defined as an answer of Yes to TEQ question 3. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH