Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks (CHANGE 2)

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT00438815
First received: February 21, 2007
Last updated: March 19, 2014
Last verified: March 2014

February 21, 2007
March 19, 2014
September 2006
March 2009   (final data collection date for primary outcome measure)
  • Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf [ Time Frame: Duration of the study (2.5 years) ] [ Designated as safety issue: No ]
  • Percent of HAE Attacks With Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.
The presence or absence of unequivocal beginning of relief of the defining symptom within 4 hours.
Complete list of historical versions of study NCT00438815 on ClinicalTrials.gov Archive Site
  • Time to Beginning of Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose 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 Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or >4.0) was not possible.
  • Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ] [ Designated as safety issue: No ]
    Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
  • Functional C1INH Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ] [ Designated as safety issue: No ]

    Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of 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 hour post-infusion ] [ Designated as safety issue: No ]
    Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.
  • Change in time to the unequivocal beginning of relief of the defining symptom for subjects who receive multiple treatments.
  • The ability of C1INH-nf concentrate to raise C1INH and C4 levels.
  • Safety will be assessed by the number and severity of adverse experiences, and changes in clinical laboratory safety parameters.
Not Provided
Not Provided
 
Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks

The study objective was to evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.

A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.

Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hereditary Angioedema
Biological: C1 esterase inhibitor [human] (C1INH-nf)
Experimental: Open-label C1INH-nf
1,000 Units (U) of C1INH-nf administered intravenously. 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)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
113
March 2009
March 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

This study was open to all subjects who:

  • Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up
  • Completed participation in LEVP2005-1/B any time after the final prophylactic therapy in Part B
  • Were enrolled but not randomized in LEVP2005-1/A after Part A was closed
  • Were excluded from LEVP2005-1 for any of the following reasons:

    • Pregnancy or lactation
    • Age less than 6 years
    • Narcotic addiction
    • Presence of anti-C1INH autoantibodies
  • Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances:

    • Had a diagnosis of HAE: evidence of a low C4 level plus either a low C1INH antigenic level or a low C1INH functional level, or
    • Had a known HAE-causing C1INH mutation, or
    • Had a diagnosis of HAE based on a strong family history of HAE as determined by the principal investigator

Exclusion Criteria:

  • History of allergic reaction to C1INH or other blood products
  • Participated in any other investigational drug study within the past 30 days
  • Received blood or a blood product in the past 60 days other than C1INH-nf
Both
1 Year and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00438815
LEVP2006-1
Not Provided
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