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: Capsule, soft
INN or Proposed INN: PHA-022121
CAS Number: 2340111-58-0
Current Sponsor code: PHA-022121
Other descriptive name: (S)-N-(1-deutero-1-(3-chlo
Sponsors
Academisch Medisch Centrum
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 • 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 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Part 1: mean symptom complex severity score (MSCS) score • Part 1: treatment outcome score (TOS) • Part 1: treatment satisfaction questionnaire for medication (TSQM) score • Part 1: number of attacks requiring rescue medication • Part 1: time to rescue medication use, if applicable • Part 2: number of investigator-confirmed moderate or severe angioedema attacks during the treatment period • Part 2: number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period • Part 2: number and proportion of days with angioedema symptoms during the treatment period • Part 2: time to first investigator-confirmed attack (i.e. duration that a patient is attack-free) in the treatment period • Part 2: angioedema quality of life (AE-QoL) questionnaire • Part 2: treatment satisfaction questionnaire for medication (TSQM) score • Part 2: angioedema control test (AECT) • Part 2: angioedema activity score (AAS);Timepoint(s) of evaluation of this end point: End points during part 1 are evaluated from the start of each of the 4 attacks untill 48 hours post-treatment. End points during part 2 are evaluated after 8 weeks of treatment with study drug and 8 weeks of treatment with placebo | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Academisch Medisch Centrum
Outcome results
None listed