A Study to Evaluate the Safety and Efficacy of Icatibant in Patients With Bradykinin Induced Angioedema

A Phase IV Clinical Study of Evaluating the Safety and Efficacy of Icatibant Injection (Icanticure) in the Treatment of Patients With Bradykinin Induced Angioedema

This is a phase IV clinical study. The investigators collect patients with a diagnosis of bradykinin induced angioedema. For a specific study period and prospectively arrange, the eligible patients who has an acute attack of angioedema could be treated by icatibant Injection (Icanticure®).

The drug, icatibant injection has been reimbursed by National Health Insurance Agency, Taiwan (NHI) in the treatment of diagnosed patients with hereditary angioedema. However, the reimbursement is still limited for some patients with atypical conditions. Therefore, Nang Kuang Company initiates a phase IV case collection study and supplies Icanticure® for free during the study period. Patients who still unable to obtain NHI's reimbursed icatibant drug is eligible for the inclusion, enter into the study and can be treated by Icanticure® to meet their clinical urgent needs. The safety and efficacy of Icanticure® are evaluated by the prospective, planed assessments in the enrolled patients.

Inclusion Criteria:

1. The male or female patient is ≥20 years old at the time of informed consent.

2. The informed consent form has been read, signed and dated by the patient.

3. At the screening visit, the investigator diagnosed bradykinin-induced angioedema based on at least one of the following:

   • Recurrent attacks of edema and/or poor respond to antihistamines, corticosteroids or epinephrine
   • Recurrent angioedema attacks of abdominal, and/or laryngeal (inclusive of laryngeal and pharyngeal) areas
   • Angioedema without the presence of urticarial rashes
   • Known family history of angioedema
   • Known to have genetic defects related to hereditary angioedema

4. Able to communicate well with the investigator, comply with study questionnaires, and other instruments used for collecting patient-reported outcomes.

Exclusion Criteria:

1. Known with a history of allergy or hypersensitivity to the investigational drug as judged by the investigator at the screening visit.

2. The patient has a diagnosis of angioedema other than bradykinin induced angioedema.

3. The patient has participated in another clinical study within the past 30 days before screening.

4. Presence of liver disease or liver injury as indicated by an abnormal liver function profile such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin, if any one of them is out of the reference range.

   The definitions of out of the reference ranges are:

   • Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or alkaline phosphatase (ALP) > 2.5 times ULN (Upper Limit Normal);
   • Serum total bilirubin >= 1.5 times ULN;

5. Presence of impaired renal function as indicated by abnormal creatinine or blood urea nitrogen values, if any one of them is out of the reference range.

   The definitions of out of the reference ranges are:

   • Creatinine clearance rate (<= 40 mL/min) (estimated by Cockcroft-Gault formula) and serum creatinine >=1.5 times ULN;
   • Blood urea nitrogen value >= 1.5 times ULN

6. Presence of impaired hematological or coagulation functions as indicated by abnormal measure values, if any one of them is out of the reference range.

7. Evidence of symptomatic coronary artery disease based on medical history, in particular, unstable angina pectoris or severe coronary heart disease.

8. Congestive heart failure (NYHA Class 3 and 4).

9. Stroke within the past 6 months.

10. Known pregnancy and/or breast-feeding.

11. In the opinion of the investigator: mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study.

12. In the opinion of the investigator: unlikely to comply with the protocol, for example, uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study for any reason.

13. In the opinion of the investigator: inability to manage study medication or self-administration of an injection.