EASSI - Evaluation of the Safety of Self-Administration With Icatibant

Open Label, Multicenter Study to Evaluate Safety, Local Tolerability, Convenience, and Efficacy of a Self-Administered Subcutaneous Formulation of Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema

This study is being conducted to explore the clinical safety, local tolerability, convenience and effectiveness of self-treatment of hereditary angioedema (HAE) attacks with subcutaneous injections of icatibant.

This Phase IIIb study was multi-center and open-label with a single dose level. Subjects with a documented diagnosis of HAE Type I or II were eligible to participate in this trial. Eligible subjects included those who had received treatment for HAE with icatibant in previous clinical trials, or subjects who had been previously treated with the marketed product Firazyr® and subjects who were naïve to icatibant treatment.

All subjects were trained on the method of self-administration at their enrollment visit (Visit 1).For the training sessions, a syringe pre-filled with 3 mL placebo solution was used in place of icatibant. Comprehensive educational material and instructions including pictograms were developed for the subjects to illustrate the method of self-administration and use of the Patient Diary. The training material provided additional information on how to self-diagnose an HAE attack and how to decide on the necessity to treat.In addition, instructions were provided on what to do in case of a laryngeal attack.

Inclusion Criteria:

Each patient must meet the following criteria to be enrolled in this study.

1. Males and females 18 years of age at the time of informed consent

2. Documented diagnosis of HAE Type I or II based on ALL of the following criteria:

   • Family and/or medical history
   • Characteristic attack manifestations, recurrent attacks
   • Historical functional C1-INH <50% normal values

3. Women of childbearing potential must use consistently and correctly a highly effective, adequate method of birth control (failure rate less than 1% per year) - sexual abstinence or have a vasectomised partner during the duration of the study. Hormonal contraception can be continued if verified by a physician that it doesn't affect the course of HAE attacks.

4. Mental and physical condition allowing patients to complete baseline assessment, to self-administer icatibant and to follow other study procedures.

5. Ability to provide signed written informed consent after all aspects of the study have been explained and discussed with the patient.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study.

1. Participation in a clinical trial of another investigational medicinal product within the past month (except a previous icatibant study).
2. Diagnosis of angioedema other than Type I or Type II HAE.
3. Evidence of symptomatic coronary artery disease based on medical history, in particular, unstable angina pectoris or severe coronary heart disease.
4. Congestive heart failure (NYHA Class 3 and 4).
5. Stroke within the past 6 months.
6. Treatment with angiotensin converting enzyme (ACE) inhibitor.
7. Pregnancy and/or breast-feeding.
8. In the opinion of the investigator: mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study.
9. 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.
10. In the opinion of the investigator: inability to manage study medication or self-administration of an injection.