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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01005888
Recruitment Status : Completed
First Posted : November 1, 2009
Results First Posted : June 3, 2010
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Tracking Information
First Submitted Date  ICMJE October 29, 2009
First Posted Date  ICMJE November 1, 2009
Results First Submitted Date  ICMJE March 17, 2010
Results First Posted Date  ICMJE June 3, 2010
Last Update Posted Date June 11, 2021
Actual Study Start Date  ICMJE March 14, 2005
Actual Primary Completion Date August 22, 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2010)
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 Measures  ICMJE
 (submitted: October 30, 2009)
The primary endpoint will be the number of attacks of angioedema during each treatment phase, using each subject as his/her own control.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2021)
  • 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 Measures  ICMJE
 (submitted: October 30, 2009)
  • 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
Current Other Pre-specified Outcome Measures
 (submitted: May 3, 2010)
Total Number of Days of Swelling During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ]
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).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Biological: C1 esterase inhibitor [human] (C1INH-nf)
  • Drug: Placebo (saline)
Study Arms  ICMJE
  • 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)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2010)
26
Original Enrollment  ICMJE
 (submitted: October 30, 2009)
20
Actual Study Completion Date  ICMJE August 22, 2007
Actual Primary Completion Date August 22, 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01005888
Other Study ID Numbers  ICMJE LEVP2005-1/Part B
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda ( Shire )
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date May 2021

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