Clinical Trial: C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: LEVP2005-1/Part B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE Attacks

Brief Summary: The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.

Detailed Summary:

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.


Sponsor: Shire

Current Primary Outcome: Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period [ Time Frame: 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).


Original Primary Outcome: The primary endpoint 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 Subject Withdrawals During Each Prophylactic Therapy Period [ Time Frame: 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 [ Time Frame: 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.
  • Average Duration of HAE Attacks During Each Prophylactic Therapy Period [ Time Frame: 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 [ Time Frame: 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.
  • Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: 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.
  • Functional C1INH Serum Levels [ Time Frame: 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).



Original Secondary Outcome:

  • Number of subjects dropping out at each stage
  • Quality of life
  • Average duration of HAE attacks
  • Number of open label C1 esterase inhibitor infusions
  • C1 esterase inhibitor levels
  • C4 levels
  • Safety will be assessed by the number and severity of adverse experiences, and changes in clinical laboratory safety parameters.
  • Average severity of HAE attacks


Information By: Shire

Dates:
Date Received: October 29, 2009
Date Started: September 2005
Date Completion:
Last Updated: March 19, 2014
Last Verified: March 2014