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

Phase 3

Completed

Conditions: Hereditary Angioedema

Interventions: Biological: C1 esterase inhibitor [human] (C1INH-nf)

Registration Number: NCT00438815

Lead Sponsor: Shire

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 113

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-label C1INH-nf	C1 esterase inhibitor [human] (C1INH-nf)	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.

Primary Outcome Measures

Name	Time	Method
Percent of HAE Attacks With Substantial Relief of the Defining Symptom	Within 4 hours after initial treatment	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.
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf	Duration of the study (2.5 years)

Secondary Outcome Measures

Name	Time	Method
Antigenic C1 Inhibitor (C1INH) Serum Levels	Pre-infusion to 1 hour post-infusion	Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Functional C1INH Serum Levels	Pre-infusion to 1 hour post-infusion	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).
Time to Beginning of Substantial Relief of the Defining Symptom	Within 4 hours after initial treatment	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.
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments	Within 4 hours after initial treatment	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.
Complement C4 Serum Levels	Pre-infusion to 1 hour post-infusion	Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.

Trial Locations

Locations (29): UCLA-David Geffen School of Medicine
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Los Angeles, California, United States
Winthrop University Hospital
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Mineola, New York, United States
Family Allergy and Asthma Center
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Atlanta, Georgia, United States
Allergy Asthma and Dermatology Research Center
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Lake Oswego, Oregon, United States
Allergy & Asthma Centre of Dayton
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Centerville, Ohio, United States
Allergy and Asthma Clinical Research, Inc
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Walnut Creek, California, United States
Institute for Asthma and Allergy
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Wheaton, Maryland, United States
Allergy and Asthma Center
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Fort Lauderdale, Florida, United States
Grand Traverse Allergy
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Traverse City, Michigan, United States
AARA Research Center
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Dallas, Texas, United States
Allergy Clinic of Tulsa
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Tulsa, Oklahoma, United States
University of Texas Medical Branch
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Galveston, Texas, United States
Baylor College of Medicine
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Houston, Texas, United States
University of California, San Diego
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San Diego, California, United States
Nevada Access to Research and Education Society
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Las Vegas, Nevada, United States
Allergy and Asthma Research Center
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San Antonio, Texas, United States
MeritCare Clinical Research
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Fargo, North Dakota, United States
Allergy and Asthma Clinic of Northwest Arkansas
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Bentonville, Arkansas, United States
Orlando Regional Healthcare
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Orlando, Florida, United States
Welborn Clinic Allergy and Immunology
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Evansville, Indiana, United States
University of Massachusetts Medical School
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Worcester, Massachusetts, United States
Penn State University
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Hershey, Pennsylvania, United States
Cornerstone Healthcare
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Parkersburg, West Virginia, United States
Mount Sinai School of Medicine
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New York, New York, United States
Marycliff Allergy Specialists
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Spokane, Washington, United States
UMDNJ Asthma and Allergy Research Center
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Newark, New Jersey, United States
Allergy and Immunology Associates
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Scottsdale, Arizona, United States
Allergy Partners of the Upstate
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Greenville, South Carolina, United States
Montefiore Medical Center
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Bronx, New York, United States