C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks
- Conditions
- Hereditary Angioedema
- Interventions
- Biological: C1 esterase inhibitor [human] (C1INH-nf)Drug: Placebo (saline)
- Registration Number
- NCT01005888
- Lead Sponsor
- Shire
- Brief Summary
The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- Documented HAE
- Normal C1q level
- Relatively frequent angioedema attacks (at least 2 per month on average)
- 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
- CROSSOVER
- Arm && Interventions
Group Intervention Description C1INH-nf First, then Placebo C1 esterase inhibitor [human] (C1INH-nf) 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. C1INH-nf First, then Placebo Placebo (saline) 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. Placebo First, then C1INH-nf C1 esterase inhibitor [human] (C1INH-nf) 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. Placebo First, then C1INH-nf Placebo (saline) 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.
- Primary Outcome Measures
Name Time Method Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period 12 weeks 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).
- Secondary Outcome Measures
Name Time Method Number of Subject Withdrawals During Each Prophylactic Therapy Period 12 weeks 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.
Average Severity of HAE Attacks During Each Prophylactic Therapy Period 12 weeks 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.
Antigenic C1 Inhibitor (C1INH) Serum Levels Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 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.
Average Duration of HAE Attacks During Each Prophylactic Therapy Period 12 weeks 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.
Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period 12 weeks 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.
Functional C1INH Serum Levels Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 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).
Trial Locations
- Locations (16)
Allergy and Asthma Clinical Research, Inc
🇺🇸Walnut Creek, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Atlanta Allergy and Asthma Clinic
🇺🇸Suwanee, Georgia, United States
Welborn Clinic Allergy and Immunology
🇺🇸Evansville, Indiana, United States
Hawaii Pacific Health Research Institute
🇺🇸Honolulu, Hawaii, United States
Nationwide Childrens Hospital Clinical Research
🇺🇸Columbus, Ohio, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Allergy Clinic of Tulsa
🇺🇸Tulsa, Oklahoma, United States
Allergy Asthma and Dermatology Research Center
🇺🇸Lake Oswego, Oregon, United States
Tyler County Hospital
🇺🇸Woodville, Texas, United States
AARA Research Center
🇺🇸Dallas, Texas, United States
St. Joseph's Hospital/Cornerstone Healthcare
🇺🇸Parkersburg, West Virginia, United States
Lake Charles Memorial Hospital
🇺🇸Lake Charles, Louisiana, United States
Allergy and Immunology Associates
🇺🇸Scottsdale, Arizona, United States
Institute for Asthma and Allergy
🇺🇸Wheaton, Maryland, United States
Libby Clinic
🇺🇸Libby, Montana, United States