Clinical Trial: Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

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

Official Title: A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Ac

Brief Summary: This study is being conducted to confirm the efficacy, safety, and immunogenicity of recombinant human C1 inhibitor (rhC1INH) at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in Hereditary Angioedema (HAE) patients.

Detailed Summary:

HAE is characterized by recurrent localized angioedema caused by uncontrolled activation of the complement and contact systems due to a congenital deficiency of functional C1 inhibitor.

rhC1INH has been developed to offer a more widely available therapeutic alternative to the existing plasma-derived C1INH (pdC1INH) products that have been used in the treatment of acute angioedema attacks patients with HAE.

Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack will be evaluated for eligibility. 75 eligible patients will be randomized (3:2) to receive an intravenous infusion of rhC1INH or saline in a double-blind fashion. Open-label rhC1INH may be provided as rescue medication to patients who do not experience the beginning of relief within 4 hours or who experience life-threatening oropharyngeal-laryngeal angioedema symptoms.

Any patient having received a randomized treatment will be allowed to receive treatment with rhC1INH in an open-label fashion for subsequent eligible attacks.


Sponsor: Pharming Technologies B.V.

Current Primary Outcome: Time to Beginning of Relief of Symptoms [ Time Frame: Patients observed for 24 hours ]

Time to beginning of relief is the time lapsed from the beginning of the infusion of study medication to the beginning of a beneficial effect based on patient's responses to the Treatmetn Effect Questionnaire (TEQ) for the primary attack location. The beginning of relief is defined as the first timepoint at which

  • The patient reports any of the following answers for TEQ question 1: "A little better", "Better" or "Much better"; and;
  • The patient reports the following answer for TEQ question 2: "Yes"; and,
  • There is persistence in improvement at the next assessment time, i.e.either the same or a better response to Question 1 and "Yes" to Question 2.


Original Primary Outcome: Time to beginning of relief based on the VAS, completed by the patient [ Time Frame: Patients observed for at least 8 hours ]

Current Secondary Outcome: Time to Minimal Symptoms [ Time Frame: 24 hours ]

The key secondary efficacy endpoint was the time to minimal symptoms at all locations. The time to achieving minimal symptoms was defined as an answer of "Yes" to TEQ question 3.


Original Secondary Outcome:

  • Minimal important difference (MID) of the overall VAS score
  • Time to beginning of relief based on the MID
  • Time to beginning of relief based on the Investigator Score
  • IgM and IgG antibodies against recombinant human C1INH (anti-rhC1INH)
  • Antibodies against host related impurities (anti-HRI)
  • Adverse events


Information By: Pharming Technologies B.V.

Dates:
Date Received: August 24, 2010
Date Started: January 2011
Date Completion:
Last Updated: August 3, 2015
Last Verified: July 2015