Clinical Trial: C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks
Brief Summary: The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.
Detailed Summary:
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.
Sponsor: Shire
Current Primary Outcome: Time to Beginning of Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ]
Original Primary Outcome:
- Part A
- The primary endpoint of Part A will be the time to the beginning of unequivocal relief of the defining symptom following initial treatment (Time 0).
- Part B
- The primary endpoint for Part B will be the number of attacks of angioedema during each treatment phase, using each subject as his/her own control.
Current Secondary Outcome:
- Number of Subjects With Beginning of Substantial Relief of the Defining Symptom [ Time Frame: 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.
- Time to Complete Resolution of the HAE Attack [ Time Frame: 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.
- Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: 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.
- Functional C1INH Serum Levels [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome:
- Part A
- The presence or absence of unequivocal beginning of relief of the defining symptom within 4 hours following treatment, the time to complete resolution of the attack, and the ability of C1INH-nf to raise C1INH and C4 levels.
- Part B
- The number of subjects dropping out at each stage, quality of life, average severity of attacks, the average duration of attacks, number of open label C1INH-nf infusions, and C1INH and C4 levels.
Information By: Shire
Dates:
Date Received: February 7, 2006
Date Started: June 2005
Date Completion:
Last Updated: March 19, 2014
Last Verified: March 2014