Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema

Study Overview
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Brief Summary
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Hereditary angioedema (HAE) is a genetic disorder characterized by sudden recurrent attacks of local swelling (angioedema). These attacks are often painful and disabling, and, in some cases, life-threatening. HAE is caused by mutations in the C1INH gene that lead to a decrease in the blood level of functional C1INH. This multi-center study was designed to assess the safety and tolerability, efficacy, and pharmacokinetics/pharmacodynamics of recombinant human C1 inhibitor (rhC1INH) in the treatment of acute hereditary angioedema attacks. Funding Source - FDA OOPD

Detailed Description
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A prospectively planned interim analysis will be performed on the double-blind data.

Official Title
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A Randomized, Placebo-controlled, Double Blind Phase II/III Study of the Safety and Efficacy of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema

Conditions
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Hereditary Angioedema, Angioneurotic Edema

Intervention / Treatment
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* Drug: Recombinant Human C1 Inhibitor
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Clear clinical and laboratory diagnosis of HAE Plasma level of functional C1INH of less than 50% of normal Acute abdominal, urogenital, peripheral, and/or oro-facial/pharyngeal/laryngeal HAE attack Main Exclusion Criteria: Acquired angioedema Pregnancy or breastfeeding Treatment with any investigational drug within prior 30 days Body weight >120 kg

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 IU/kg rhC1INH<br>100 IU/kg Recombinant human C1 inhibitor | Drug: Recombinant Human C1 Inhibitor<br>* IV<br>* Other names: conestat alfa;|
| Experimental: 50 IU/kg rhC1INH<br>50 IU/kg Recombinant human C1 inhibitor | Drug: Recombinant Human C1 Inhibitor<br>* IV<br>* Other names: conestat alfa;|
| Placebo Comparator: Saline<br> | Drug: placebo<br>* saline solution<br>* Other names: physiological salt solution;|

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 | The time to beginning of relief of symptoms at the location that showed the first visual analogue scale (VAS) score decrease of at least 20 mm from baseline score with persistence to the next timepoint, assessment timepoints were taken on pre-scheduled time-points after study drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to beginning of relief has been calculated as median time, by using the exact timepoints on which each assessment was performed. | up to 48 hours after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Minimal Symptoms | The time to minimal symptoms was the time to minimal symptoms for an attack, assessed using the Visual Analogue Scale (VAS) score. Symptoms were said to be minimal when the VAS score at all locations was below 20 mm. Assessment timepoints were: baseline, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to minimal symtoms has been calculated by using the exact timepoints on which each assessment was performed. | up to 48 hours after study drug administration |