Acquired angioedema due to C1-inhibitor deficiency MedDRA version: 21.0 Level: PT Classification code 10081035 Term: Acquired C1 inhibitor deficiency System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Name: PHA-022121
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PHA-022121 Monohydrate
Current Sponsor code: PHA-022121 Monohydrate
Other descriptive name: Deucrictibant
Concentr
Sponsors
Academisch Medisch Centrum
Eligibility
Sex/Gender
All
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 =65 years) no F.1.3.1 Number of subjects for this age range 1
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 |
|---|---|
| Main Objective: To evaluate the efficacy of long-term prophylactic treatment with deucrictibant (PHA-022121) once daily in preventing angioedema attacks in patients with acquired C1 inhibitor deficiency. ;Secondary Objective: To evaluate the safety of long-term prophylactic use of deucrictibant (PHA-022121) and to further explore the clinical efficacy of deucrictibant (PHA-022121) with regard to quality of life, treatment satisfaction and frequency and timing of on demand medication use. ;Primary end point(s): Normalized number of investigator-confirmed angioedema attacks;Timepoint(s) of evaluation of this end point: Normalized number of investigator-confirmed angioedema attacks per four weeks of exposure compared to baseline (deucrictibant (PHA-022121) naive participants) or before treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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 before treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants) in the Angioedema Control Test (AECT) • Change from baseline (deucrictibant (PHA-022121) naïve patients) or change from before first prophylactic treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants) in the Angioedema Quality of Life (AE-QoL) after completion of the treatment period • AE-QoL-score at 1, 3, 6, 9 and 12 months • Treatment satisfaction questionnaire for Medication (TSQM) at 1, 3, 6, 9 and 12 months • 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 ;Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated after 12 months of treatment. | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Academisch Medisch Centrum
Outcome results
None listed