Hereditary angioedema (HAE). Hereditary angioedema (HAE). Attacks in patients with hereditary angioedema(HAE) due to C1 esterase inhibitor deficiency. MedDRA version: 14.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Ruconest
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: conestat alfa
CAS Number: 80295-38-1
Current Sponsor code: rhC1INH
Concentration unit: U unit(s)
Concent
Sponsors
PHARMING TECHNOLOGIES B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria: 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate 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 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 at the primary attack location, defined as the time between beginning of treatment administration and the first time point at which: o The patient reports the following answers for TEQ Question 1: “A little better”, Better” or “Much better; and, o The patient reports the following answer for TEQ Question 2: “Yes”; and, o There is persistence of improvement at the next assessment time, i.e., either the same or a better response to Question 1 and “Yes” to Question 2).;Timepoint(s) of evaluation of this end point: The primary end point will be assessed by TEQ for each symptomatic anatomical location at the following time points: 0 (just before study medication administration), 15 min, 30 min, 45 min, 60 min, 75 min, 90 min, 105 min, 2, 2 ½ , 3, 3 ½, 4, 4 ½, 5, 5 ½, and 6 hours. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy variable: Time to minimal symptoms defined as the time between beginning of treatment administration and the first time point at which the patient provides an affirmative response to Question 3 of the TEQ at all symptomatic locations;Timepoint(s) of evaluation of this end point: The secondary end point will be assessed by TEQ for each symptomatic anatomical location at the following time points: 0 (just before study medication administration), 15 min, 30 min, 45 min, 60 min, 75 min, 90 min, 105 min, 2, 2 ½ , 3, 3 ½, 4, 4 ½, 5, 5 ½, and 6 hours. | — |
Countries
Argentina, Hungary, Italy, Macedonia, the former Yugoslav Republic of, South Africa, United States
Contacts
Public ContactELISABETTA ZUCCATO
CMED (CLINICAL RESEARCH SERVICES) LTD
Outcome results
None listed