C1 Esterase Inhibitor (C1INH-nf) for the Prevention 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 prevention of acute HAE attacks.

Detailed Description
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Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity). The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures). A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed to placebo.

Official Title
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LEVP2005-1/Part B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE 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 Relatively frequent angioedema attacks (at least 2 per month on average) 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C1INH-nf First, then Placebo<br>1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. | Biological: C1 esterase inhibitor [human] (C1INH-nf)<br> <br> Drug: Placebo (saline)<br> <br> |
| Experimental: Placebo First, then C1INH-nf<br>Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. | Biological: C1 esterase inhibitor [human] (C1INH-nf)<br> <br> Drug: Placebo (saline)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period | An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subject Withdrawals During Each Prophylactic Therapy Period | At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record. | 12 weeks | 
| Average Severity of HAE Attacks During Each Prophylactic Therapy Period | All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period. | 12 weeks | 
| Average Duration of HAE Attacks During Each Prophylactic Therapy Period | The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of no swelling at all five locations. | 12 weeks | 
| Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period | The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures. | 12 weeks | 
| Antigenic C1 Inhibitor (C1INH) Serum Levels | Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 | 
| Functional C1INH Serum Levels | Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH). | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 | 

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