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

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ClinicalTrials.gov Identifier: NCT00289211
Recruitment Status : Completed
First Posted : February 9, 2006
Results First Posted : June 2, 2010
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Tracking Information
First Submitted Date  ICMJE February 7, 2006
First Posted Date  ICMJE February 9, 2006
Results First Submitted Date  ICMJE March 17, 2010
Results First Posted Date  ICMJE June 2, 2010
Last Update Posted Date June 11, 2021
Actual Study Start Date  ICMJE March 14, 2005
Actual Primary Completion Date April 13, 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2010)
Time to 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2006)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2021)
  • 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 Measures  ICMJE
 (submitted: February 7, 2006)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
Official Title  ICMJE 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 Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Biological: C1 esterase inhibitor [human] (C1INH-nf)
  • Drug: Placebo (saline)
Study Arms  ICMJE
  • Experimental: C1INH-nf
    1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
    Intervention: Biological: C1 esterase inhibitor [human] (C1INH-nf)
  • Placebo Comparator: Placebo
    Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered.
    Intervention: 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)
83
Original Enrollment  ICMJE
 (submitted: February 7, 2006)
70
Actual Study Completion Date  ICMJE April 13, 2007
Actual Primary Completion Date April 13, 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented HAE
  • Normal C1q level

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 NCT00289211
Other Study ID Numbers  ICMJE LEVP2005-1/Part A
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 June 2021

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