C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
- Conditions
- Hereditary Angioedema
- Interventions
- Drug: Placebo (saline)Biological: C1 esterase inhibitor [human] (C1INH-nf)
- Registration Number
- NCT00289211
- Lead Sponsor
- Shire
- Brief Summary
The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
- Documented HAE
- Normal C1q level
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo (saline) 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. C1INH-nf C1 esterase inhibitor [human] (C1INH-nf) 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.
- Primary Outcome Measures
Name Time Method Time to Beginning of Substantial Relief of the Defining Symptom Within 4 hours after initial treatment 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects With Beginning of Substantial Relief of the Defining Symptom Within 4 hours after initial treatment 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.
Antigenic C1 Inhibitor (C1INH) Serum Levels Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.
Time to Complete Resolution of the HAE Attack 72 hours 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.
Functional C1INH Serum Levels Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion 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).
Complement C4 Serum Levels Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.
Trial Locations
- Locations (37)
Allergy and Asthma Center
🇺🇸Fort Lauderdale, Florida, United States
Allergy Partners of the Upstate
🇺🇸Greenville, South Carolina, United States
St. Louis University School of Medicine
🇺🇸Saint Louis, Missouri, United States
UCLA-David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Optimed Research
🇺🇸Columbus, Ohio, United States
The Baton Rouge Clinic, AMC
🇺🇸Baton Rouge, Louisiana, United States
Allergy Clinic of Tulsa
🇺🇸Tulsa, Oklahoma, United States
Allergy and Asthma Clinical Research, Inc
🇺🇸Walnut Creek, California, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Grand Traverse Allergy
🇺🇸Traverse City, Michigan, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Penn State University
🇺🇸Hershey, Pennsylvania, United States
Institute for Asthma and Allergy
🇺🇸Wheaton, Maryland, United States
Family Allergy and Asthma Center
🇺🇸Atlanta, Georgia, United States
Puget Sound Allergy, Asthma and Immunology
🇺🇸Tacoma, Washington, United States
Welborn Clinic Allergy and Immunology
🇺🇸Evansville, Indiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Allergy and Asthma Research Center
🇺🇸San Antonio, Texas, United States
Allergy and Immunology Associates
🇺🇸Scottsdale, Arizona, United States
Clinical Research Consultants, Inc
🇺🇸Hoover, Alabama, United States
University of Iowa Hospital and Clinic
🇺🇸Iowa City, Iowa, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
MeritCare Clinical Research
🇺🇸Fargo, North Dakota, United States
Allergy Asthma and Dermatology Research Center
🇺🇸Lake Oswego, Oregon, United States
Marycliff Allergy Specialists
🇺🇸Spokane, Washington, United States
AARA Research Center
🇺🇸Dallas, Texas, United States
Bernstein Clinical Research
🇺🇸Cincinnati, Ohio, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
UMDNJ Asthma and Allergy Research Center
🇺🇸Newark, New Jersey, United States
Nevada Access to Research and Education Society
🇺🇸Las Vegas, Nevada, United States
Orlando Regional Healthcare
🇺🇸Orlando, Florida, United States
Virginia Adult and Pediatric Allergy and Asthma
🇺🇸Richmond, Virginia, United States
Allergy, Asthma and Pulmonary Clinical Research
🇺🇸Madison, Wisconsin, United States
Allergy Asthma and Immunology
🇺🇸Falmouth, Massachusetts, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States