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

• Register: EUCTR
• Last refreshed on: 6 May 2013
• Main ID: EUCTR2011-000049-19-HU
• Date of registration: 08/02/2011
• Prospective Registration: Yes
• Primary sponsor: Pharming Technologies B.V.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 01/04/2011
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000049-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: with an open-label extension phase If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary, Italy

Key inclusion & exclusion criteria

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 by 20 mm or more at any eligible site.

Inclusion Criteria for Open Label Treatment:
1. Above screening and randomization criteria continue to be met for subsequent eligible attack.
2. 24 hours have passed since the patient’s randomized or last open-label treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion Criteria at Screening:
Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit dander IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent).
1. A diagnosis of acquired C1INH deficiency (AAE)
2. Pregnancy, or breastfeeding, or current intention to become pregnant
3. Treatment with any investigational drug in the past 30 days
4. Any clinically significant abnormality in the routine hematology and biochemistry that, in the opinion of the investigator, might interfere with the evaluation of study objectives
5. Any condition or treatment that, in the opinion of the investigator, might interfere with the evaluation of study objectives

Exclusion Criteria for randomized treatment:
1. Any changes since screening that would exclude patient based on above exclusion
criteria
2. Positive pregnancy test (urine or serum).

Exclusion Criteria for Open Label Treatment:
1. Any changes since screening that would exclude subject based on above exclusion
criteria.
2. Positive pregnancy test (urine or serum).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of acute angioedema attacks in patients with hereditary angioedema (HAE).
MedDRA version: 12.1 Level: LLT Classification code 10019860 Term: Hereditary angioedema

Intervention(s)

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

Primary Outcome(s)

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.

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.

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 ID(s)

C1 1310