A Phase IIIb 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 acute attacks of angioedema in patients with HAE - Phase III study of recombinant human C1 inhibitor

INTERVENTION: Trade Name: Ruconest 2100 U powder for solution for injection Product Name: Recombinant human C1 inhibitor Product Code: rhC1INH Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: conestat alfa Current Sponsor code: rhC1INH Other descriptive name: recombinant human C1 inhibitor Concentration unit: U unit(s) Concentration type: equal Concentration number: 2100‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Treatment of acute angioedema attacks in patients with hereditary angioedema (HAE). ; MedDRA version: 12.1 Level: LLT Classification code 10019860 Term: Hereditary angioedema PRIMARY OUTCOME: Main Objective: To confirm efficacy and safety of rhC1INH at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in patients with HAE.; Primary end point(s): ‐ Primary efficacy variable: Time to beginning of relief, defined as the time between baseline (beginning of treatment administration) and the first time point at which the ‘overall severity VAS’ decreases by at least the MID at any eligible location, with persistence of the decrease at the next assessment time so that for the next value at the location a decrease of at least the MID with respect to baseline is also observed. Sensitivity analyses of the time to beginning of relief will be performed using the other two estimates of the MID above and using a decrease of 20mm or greater, as defined in previous studies with rhC1INH. ; ‐ Time to minimal symptoms defined as the time between baseline (beginning of treatment administration) and the first time point at which the ‘overall severity VAS’ decreases to a value less than the MID (as identified in the above estimates and for 20 mm), at all locations.; Secondary Objective: ‐ To estimate the minimal important difference (MID) of the visual analogue scale (VAS) score used in the assessment of patient‐reported outcomes during an acute attack of angioedema in patients with HAE.; ‐ To assess efficacy, safety and immunogenicity of rhC1INH when used for the repeat treatment of acute angioedema attacks in patients with HAE.; INCLUSION CRITERIA: Inclusion Criteria at Screening: 1. Aged at least 18 years 2. Signed written informed consent 3. Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal 4. Willingness and ability to comply with all protocol procedures Inclusion Criteria for randomized treatment: 1. Above screening criteria continue to be met 2. Clinical symptoms of HAE attack 3. Onset of symptoms less than 5 hours before the time at which medical evaluation determined eligibility for inclusion 4. ‘Overall severity VAS’ score for at least one anatomical location at the time of initial evaluation and Time 0 of at least 50 mm 5. No evidence of regression of angioedema symptoms scored with VAS at t = 0 h compared with VAS score at the time of initial evaluation, i.e. no decrease in symptoms of angioedema scored with overall VAS at t = 0 h compared with score at the time of initial evaluation