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 leads to a decrease in the blood level of functional C1INH. This multi-center study was designed to assess the safety and tolerability, efficacy and pharmacodynamics/ pharmacokinetics of recombinant human C1 inhibitor (rhC1INH) in the treatment of acute hereditary angioedema attacks.

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 III Study of the Efficacy and Safety 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, Genetic Disorders

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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Inclusion Criteria: Clear clinical and laboratory diagnosis of HAE Baseline plasma level of functional C1INH of less than 50% of normal Evidence for exacerbation or development of a severe abdominal, oro-facial/ pharyngeal/ laryngeal, genito-urinary and/or peripheral HAE attack Exclusion Criteria: Acquired angioedema Pregnancy or breastfeeding Participation in another clinical study within prior 3 months

Ages Eligible for Study
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Minimum Age: 16 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;|
| Placebo Comparator: Saline<br>Saline solution | Drug: Placebo<br>* IV<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 has been assessed by using a patient-reported visual analogue scale (VAS) ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first VAS score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points 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 time-points were: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to minimal symptoms has been calculated by using the exact time-points on which each assessment was performed. | up to 48 hours after study drug administration |