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

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT01005888
First received: October 29, 2009
Last updated: March 19, 2014
Last verified: March 2014

October 29, 2009
March 19, 2014
September 2005
May 2007   (final data collection date for primary outcome measure)
Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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).
The primary endpoint will be the number of attacks of angioedema during each treatment phase, using each subject as his/her own control. [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01005888 on ClinicalTrials.gov Archive Site
  • Number of Subject Withdrawals During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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).

  • Number of subjects dropping out at each stage [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Average duration of HAE attacks [ Designated as safety issue: No ]
  • Number of open label C1 esterase inhibitor infusions [ Designated as safety issue: No ]
  • C1 esterase inhibitor levels [ Designated as safety issue: No ]
  • C4 levels [ Designated as safety issue: No ]
  • Safety will be assessed by the number and severity of adverse experiences, and changes in clinical laboratory safety parameters. [ Designated as safety issue: Yes ]
  • Average severity of HAE attacks [ Designated as safety issue: Yes ]
Total Number of Days of Swelling During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
A day of swelling was defined as a day that a subject reported swelling at any of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity).
Not Provided
 
C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks
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

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Hereditary Angioedema
  • Biological: C1 esterase inhibitor [human] (C1INH-nf)
  • Drug: Placebo (saline)
  • Experimental: C1INH-nf First, then Placebo
    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.
    Interventions:
    • Biological: C1 esterase inhibitor [human] (C1INH-nf)
    • Drug: Placebo (saline)
  • Experimental: Placebo First, then 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.
    Interventions:
    • Biological: C1 esterase inhibitor [human] (C1INH-nf)
    • Drug: Placebo (saline)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
August 2007
May 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Documented HAE
  • Normal C1q level
  • Relatively frequent angioedema attacks (at least 2 per month on average)

Exclusion Criteria:

  • 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
Both
6 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01005888
LEVP2005-1/Part B
Yes
Chief Scientific Officer, ViroPharma
Shire
Not Provided
Principal Investigator: Bruce Zuraw, MD University of California, San Diego
Shire
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP