Acute treatment and prophylaxis for acquired angioedema
- Conditions
- Acquired angioedema due to C1-inhibitor deficiencyMedDRA version: 21.0Level: PTClassification code 10081035Term: Acquired C1 inhibitor deficiencySystem Organ Class: 10040785 - Skin and subcutaneous tissue disordersTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2021-000720-36-NL
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 3
In order to be eligible to participate in this study, a patient must meet all of the following criteria:
•Provision of signed and dated informed consent form
•Male or female, aged > 35 at enrollment
•Diagnosis of AAE-C1-INH based upon all of the following:
1.Documented clinical history consistent with AAE-C1-INH (subcutaneous or mucosal, nonpruritic swelling without accompanying urticarial and C1-INH activity < 0.63mE/L)
2.At least one of the following:
•Age at reported onset of first angioedema symptoms = 40 years AND family history negative for angioedema
•C1q below lower limit of normal (88 kU/L) AND absence of SERPING1 mutation
•Serological confirmation of antibodies against C1-INH
•Documented history of at least three angioedema attacks in the last 4 months, or at least two angioedema attacks in the last 2 months.
•Reliable access and experience to use icatibant to effectively manage acute angioedema attacks
•Female patients of childbearing potential must agree to be abstinent or to use highly effective forms of contraception methods from enrollment through the end of the study. This includes progestin-only oral contraceptive associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD, all types) or intrauterine hormone releasing systems (IUS). A female of childbearing potential whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.
•Male patients, including males who are surgically sterile (post vasectomy), who have a female partner of childbearing potential must agree to be sexually abstinent or use a medically acceptable form of barrier contraception for 2 weeks after each administration of study drug. In addition, they must agree to not donate sperm during study participation.
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 2
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
Patients who meet any of the following criteria will be excluded from the study:
•Pregnancy or breast-feeding
•Clinically significant abnormal ECG, most notably a QTcF > 470 ms (for females) or > 450 ms (for males)
•Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, or any other cardiovascular abnormality within the previous year
•Any other systemic disease (e.g., gastrointestinal, renal, respiratory, neurological) or significant disease or disorder that would interfere with the patient’s safety or ability to participate in the study
•Active infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) or hepatitis C virus (HCV)
•History of abnormal hepatic function (AST > 2×ULN, ALT > 2×ULN, or total bilirubin > 1.5×ULN)
•History of abnormal renal function (eGFR CKD-EPI < 60 mL/min/1.73 m2)
•History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > 3 drinks/day)
•History of documented severe hypersensitivity to any medicinal product
•Participation in any other investigational drug study currently, within the last 30 days or within 5 half-lives of study drug at enrollment (whichever was longer)
•Regular use of corticosteroids, antihistamines, narcotics, and other pain relief medications for acute angioedema attack treatment
•Use of concomitant medication that are moderate or potent inhibitors/inducers of CYP3A4 or are metabolized by CYP3A4 and have a narrow therapeutic range, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit as well as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids (not for topical use or inhalation)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: To further explore the clinical efficacy of PHA-022121 versus placebo with regard to onset of symptom relief, time to complete symptom relief, to evaluate the frequency and timing of rescue medication use, and to evaluate the safety of PHA-022121 versus placebo. ;Primary end point(s): •Part 1: 3-symptom composite visual analogue scale (VAS-3) score <br>•Part 2: number of investigator-confirmed angioedema attacks ;Timepoint(s) of evaluation of this end point: Part 1: VAS-3 is measured from the start of each of the 4 attacks untill 48 hours post-treatment<br>Part 2: number of attacks during 8 weeks of treatment with study drug and 8 weeks of treatment with placebo;Main Objective: To evaluate the efficacy of three different single doses of PHA-022121 versus placebo in achieving angioedema symptom relief during acute attacks and the efficacy of prophylactic treatment with PHA-022121 versus placebo in preventing breakthrough angioedema attacks in patients with acquired C1 inhibitor deficiency.
- Secondary Outcome Measures
Name Time Method