A Phase III randomized, double-blind, placebocontrolled 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
- Conditions
- Hereditary angioedema (HAE). Hereditary angioedema (HAE). Attacks in patients with hereditary angioedema(HAE) due to C1 esterase inhibitor deficiency.MedDRA version: 14.1Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2011-000049-19-IT
- Lead Sponsor
- PHARMING TECHNOLOGIES B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 75
Screening Inclusion Criteria: 1. Age 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 at eligible attack location (abdominal, peripheral, facial, or oropharyngeal-laryngeal) less than 5 hours before the time at which initial 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 is 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 the primary attack location. Inclusion Criteria for Open Label Treatment for subsequent angioedema attacks: 1. Above screening and randomization criteria continue to be met for subsequent eligible attack. (Any anatomical location of HAE attack, including urogenital, may be treated in the open-label phase of the study provided it meets the other criteria stated above with respect to onset, severity, and lack of regression.) 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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
Exclusion Criteria at Screening: 1. Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit epithelium (dander) IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent). 2. A diagnosis of acquired C1INH deficiency (AAE) 3. Pregnancy, or breastfeeding, or current intention to become pregnant 4. Treatment with any investigational drug in the past 30 days 5. Any clinically significant abnormality in the study-specific hematology, biochemistry that, in the opinion of the investigator, might interfere with the evaluation of study objectives 6. Any condition or treatment that, in the opinion of the investigator, might interfere with the evaluation of study objectives 7. Known or suspected addiction to drug and/or alcohol abuse Exclusion Criteria for Randomized treatment: 1. Any changes since screening that would exclude patient based on above exclusion criteria 2. Suspicion for an alternate explanation of the symptoms other than acute HAE attack 3. Blood in urine (for patients with abdominal symptoms only) 4. Blood in stool (for patients with abdominal symptoms only) 5. Fever (oral temp > 38° C) 6. Positive pregnancy test (urine or serum). Patients with life-threatening symptoms (e.g. a laryngeal attack with respiratory and/or cardiovascular compromise) should be immediately treated with any medication or procedure (including intubation, tracheostomy) deemed necessary and effective treatment should not be postponed because of randomization procedures or possibility of being randomized to placebo. Exclusion Criteria for Open label Treatment: 1. Any changes since screening that would exclude subject based on above exclusion criteria. 2. Suspicion for an alternate explanation of the symptoms other than acute HAE attack 3. Blood in urine (for patients with abdominal symptoms only) 4. Blood in stool (for patients with abdominal symptoms only) 5. Fever (oral temp > 38° C) 6. Positive pregnancy test (urine or serum). 7. Positive anti-rabbit epithelium (dander) IgE test (cut off >0.35 kU/L; ImmunoCap assay; Phadia or equivalent)(performed at a previous D28 visit)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method