Open-Label 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 evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.

Detailed Description
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A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.

Official Title
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LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks

Conditions
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Hereditary Angioedema

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: This study was open to all subjects who: Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up Completed participation in LEVP2005-1/B any time after the final prophylactic therapy in Part B Were enrolled but not randomized in LEVP2005-1/A after Part A was closed Were excluded from LEVP2005-1 for any of the following reasons: Pregnancy or lactation Age less than 6 years Narcotic addiction Presence of anti-C1INH autoantibodies Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances: Had a diagnosis of HAE: evidence of a low C4 level plus either a low C1INH antigenic level or a low C1INH functional level, or Had a known HAE-causing C1INH mutation, or Had a diagnosis of HAE based on a strong family history of HAE as determined by the principal investigator Exclusion Criteria: History of allergic reaction to C1INH or other blood products Participated in any other investigational drug study within the past 30 days Received blood or a blood product in the past 60 days other than C1INH-nf

Ages Eligible for Study
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Minimum Age: 1 Year

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label C1INH-nf<br>1,000 Units (U) of C1INH-nf administered intravenously. 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> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf |  | Duration of the study (2.5 years) | 
| Percent of HAE Attacks With Substantial Relief of the Defining Symptom | Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments. | Within 4 hours after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Beginning of Substantial Relief of the Defining Symptom | Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose 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 Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments | For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or >4.0) was not possible. | Within 4 hours after initial treatment | 
| Antigenic C1 Inhibitor (C1INH) Serum Levels | Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug. | Pre-infusion to 1 hour post-infusion | 
| Functional C1INH Serum Levels | Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of 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 hour post-infusion | 
| Complement C4 Serum Levels | Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug. | Pre-infusion to 1 hour post-infusion | 

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