C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks

Study Overview
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Brief Summary
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The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.

Detailed Description
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Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary. The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures. A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.

Official Title
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LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: C1 esterase inhibitor [human] (C1INH-nf)
* Drug: Placebo (saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HAE Normal C1q level Exclusion Criteria: Low C1q level B-cell malignancy Presence of anti-C1INH autoantibody History of allergic reaction to C1INH or other blood products Narcotic addiction Current participation in any other investigational drug study or within the past 30 days Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days Pregnancy or lactation Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study

Ages Eligible for Study
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Minimum Age: 6 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: C1INH-nf<br>1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. | Biological: C1 esterase inhibitor [human] (C1INH-nf)<br> <br> |
| Placebo Comparator: Placebo<br>Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered. | Drug: Placebo (saline)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Beginning of Substantial Relief of the Defining Symptom | Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments. | Within 4 hours after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Beginning of Substantial Relief of the Defining Symptom | Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments. | Within 4 hours after initial treatment | 
| Time to Complete Resolution of the HAE Attack | Randomized subjects were contacted 72-96 hours (3-4 days) after discharge from the study site to determine when complete resolution of the HAE attack occurred. | 72 hours | 
| Antigenic C1 Inhibitor (C1INH) Serum Levels | Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug. | Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion | 
| Functional C1INH Serum Levels | Percent change in functional C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH). | Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion | 
| Complement C4 Serum Levels | Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug. | Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE, Hereditary angioedema, C1 esterase inhibitor (human), C1INH-nf