Acquired C1-inhibitor deficiency
Conditions
Interventions
Patients will receive 40 mg of deucrictibant (PHA-022121) in an
extended-release (XR) tablet once daily for a maximum of 20 months.
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Provision of signed and dated informed consent form - Male or female, aged >= 35 at enrolment - Diagnosis of AAE-C1-INH based upon all of the following: 1. Documented clinical history consistent with AAE-C1-INH (subcutaneous or mucosal, nonpruritic swellings without accompanying urticaria and C1-INH activity = 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 four months, or at least two angioedema attacks in the last two months. For patients that previously participated in POP-AID part 2, a historical attack-rate of at least three attacks in four months or two attacks in two months previous to the start of POP-AID part 2 is required • Reliable access to and experience with using 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 enrolment 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 two weeks after each administration of study drug. In addition, they must agree to not donate sperm during study participation.
Exclusion criteria
Exclusion criteria: • 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 three drinks/day) • History of documented severe hypersensitivity to any medicinal product • Participation in any investigational drug study within five half-lives of study drug at enrolment • 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Normalized number of investigator-confirmed angioedema attacks per 28 days of exposure compared to baseline (deucrictibant (PHA-022121) naive participants) or compared to baseline of the POP-AID study (previous POP-AID participants) | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: • Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period • Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period • Duration in days of the longest attack free interval • Change from baseline (deucrictibant (PHA-022121) naïve patients) or change from baseline of POP-AID (previous POP-AID participants) in Angioedema Control Test (AECT) score • Change from baseline (deucrictibant (PHA-022121) naïve patients) or change from baseline POP-AID (previous POP-AID participants) in Angioedema Quality of Life (AE-QoL) score after completion of the treatment period • AE-QoL-score at 1, 3, 6, 9, 12, 15, 18 and 20 months • Treatment satisfaction questionnaire for Medication (TSQM) score at 1, 3, 6, 9, 12, 15, 18 and 20 months Safety: Occurrence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (AEs), and treatment-emergent serious adverse events (TESAEs), including clinically significant changes in clinical laboratory tests, vital signs or ECG reported as AE until the end of the study. | — |
Countries
Netherlands
Outcome results
None listed