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

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

Official Title: LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-

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

Detailed Summary: 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.
Sponsor: Shire

Current Primary Outcome:

• Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf [ Time Frame: Duration of the study (2.5 years) ]
• Percent of HAE Attacks With Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ]
  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.

Original Primary Outcome: The presence or absence of unequivocal beginning of relief of the defining symptom within 4 hours.

Current Secondary Outcome:

• Time to Beginning of Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ]
  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 ]
  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 ]
  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 ]

  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 ]
  Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.

Original Secondary Outcome:

• 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.

Dates:
Date Received: February 21, 2007
Date Started: September 2006
Date Completion:
Last Updated: March 19, 2014
Last Verified: March 2014