Oral Deucrictibant for Prophylactic and Acute Treatment in Hereditary Angioedema Patients

Inclusion criteria

• Provision of written informed consent.
• Male or female, aged ≥18 at the time of provision of informed consent.
• Diagnosis of bradykinin-mediated angioedema based upon all of the following:
• Clinical history consistent with angioedema (subcutaneous or mucosal, nonpruritic swelling without accompanying urticaria), not responsive to treatments of anti-histamine, corticosteroid, and/or omalizumab.
• Tried and failed at least 2 weeks of cetirizine 20 mg twice a day (or its equivalent alternative antihistamines, such as fexofenadine, loratadine, desloratadine or levocetirizine, etc.).
• Total blood BK peptide levels following 3 days cold activation is above the diagnostic value in non-attack and/or attack period\*. \*The "attack period" is defined as within 24 hours after an attack.
• Documented diagnostic testing results: C1INH antigen concentration and functional activity within normal range; C4 antigen concentration within normal range.
• Documented history of at least 2 angioedema attacks in the previous 2 months.
• Reliable access and experience to use standard of care medication to effectively manage acute angioedema attacks.

Exclusion criteria

• Any diagnosis of angioedema other than BK-AE-nC1INH.
• Participation in a clinical study with any other investigational drug within the previous 30 days or within 5 half-lives of the investigational drug at Screening (whichever was longer).
• Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks of Screening.
• Receiving prophylactic treatment for BK-AE-nC1INH. Participants who have previously received prophylactic therapy but have stopped can participate in this study provided a sufficiently long washout period (≥5 half-life) is observed before the participant is screened. Exclusion includes use of: • Short-term prophylaxis for BK-AE-nC1INH within 7 days prior to Screening.
• Any females who are pregnant, plan to become pregnant, or are currently breast-feeding.
• Abnormal hepatic function (aspartate aminotransferase \>2× upper limit of normal, alanine aminotransferase \>2× ULN, or total bilirubin \>1.5× upper limit of normal). Participants with Gilbert's syndrome, defined as isolated increase of total bilirubin ≤3× upper limit of normal and aspartate aminotransferase and alanine aminotransferase within the normal range, are not excluded.
• Abnormal renal function (estimated glomerular filtration rate \[eGFR\] \<60 mL/min/1.73 m2).
• Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension, bradycardia, or any other clinically significant cardiovascular abnormality within the previous year that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study.
• History of epilepsy and other significant neurological diseases.
• Any clinically significant gastrointestinal dysfunction (eg, diarrhea, inflammatory bowel disease) which may impact on study drug absorption.
• History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
• Use of concomitant medications with systemic absorption that are moderate and strong inhibitors or strong inducers of CYP3A4, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, and grapefruit juice as well as carbamazepine, and rifampin within the last 30◦days or within 5◦half-lives (whichever is longer) of the time of randomization.
• Known hypersensitivity to deucrictibant or any of the excipients of study drug.