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

Phase 3

Completed

• Conditions: Hereditary Angioedema
• Interventions: Drug: Icatibant

• Registration Number: NCT00997204
• Lead Sponsor: Shire

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2009-09-25
• Study First Submitted: 2009-10-16
• Study First Submitted QC: 2009-10-16
• Study First Posted: 2009-10-19
• Primary Completion: 2011-06-22
• Study Completion: 2011-06-22
• Results First Submitted: 2013-11-04
• Results First Submitted QC: 2014-06-30
• Results First Posted: 2014-07-28
• Status Verified: 2021-05
• Last Update Submitted: 2021-06-01
• Last Update Posted: 2021-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 151

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
icatibant- Self administration Phase	Icatibant	Single subcutaneous injection of icatibant, 30 mg
Icatibant- Naive Treatment Phase	Icatibant	Single subcutaneous injection of icatibant, 30 mg

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant	7 days from the beginning of each phase	Clinical safety of self-treatment of acute HAE attacks with s.c. injections of icatibant was assessed by calculating the number of AEs occurred during the study. Only those adverse events occurring up to the earlier of 7 days from the start of the naive phase, study discontinuation and start of the self-administration phase are assessed. The Local Tolerability Assessment tool was used. Subjects and Investigators graded erythema/reddening, swelling, burning, pruritus/itching, warm sensation, and skin pain on a 0 to 3 severity scale.

Secondary Outcome Measures

Name	Time	Method
Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort	48 hours post-dose	Subjects assessed angioedema attack symptoms using the visual analogue scale (VAS) for skin pain, skin swelling and abdominal pain. The VAS is a continuous scale comprised of a 100 mm in length line, anchored by 2 verbal descriptors, one for each symptom extreme 0 (no pain) and 100 (worst pain). The respondent is asked to place a mark on the VAS line (any where between 0 and 100 mm) at the point that represents their pain intensity. The score is determined by measuring the distance (mm) on the line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. Score interpretation is: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). Symptom relief is defined as at least a 50% reduction in a pre-dose VAS score of 30 mm or greater. The time to onset of symptom relief is defined as the first of 3 consecutive assessments at which symptom relief was observed.

Trial Locations

Locations (26)

Hospital Britanico Unidad de Alergia; 🇦🇷 Buenos Aires, Argentina

Universitätsklinik für Dermatologie und Venerologie; 🇦🇹 Graz, Austria

Tel Aviv Sourasky Medical Center - Allergy Unit; 🇮🇱 Tel Aviv, Israel

Luzerner Kantonsspital; 🇨🇭 Luzern, Switzerland

Odense Universitetshospital-OUH; 🇩🇰 Odense, I Og Alergicentret, Denmark

Hospital Edouaed Herriot; 🇫🇷 Lyon, Cedex 03, France

Clinique Universitaire de Medicine/ Centre National de reference; 🇫🇷 Grenoble, Grenoble Cedex 09, France

Ospedale Luigi Sacco; 🇮🇹 Milano, Italy

Hopital Claude Huriex/ Service de medicine interne; 🇫🇷 Lille, Lille Cedex, France

Hospital Universitario Vall de Hebrón / Sección de Alergia, Escola Infermeria; 🇪🇸 Barcelona, Spain

Hospital Universitario La Paz, Servicio de Alergia; 🇪🇸 Madrid, Spain

Hospital Universitario La Fe, Servicio de Alergia; 🇪🇸 Valencia, Spain

Centre Hospitalier Universitaire/ Service de Dermatologie; 🇫🇷 Angers, Angers Cedex 09, France

Hautklinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität; 🇩🇪 Mainz, Germany

Bnai-Zion M.C. Clinical Immunology and Allergy Division; 🇮🇱 Haifa, Israel

Southmead Hospital, Department of Immunology; 🇬🇧 Bristol, United Kingdom

The Chaim Sheba Medical Center, The Allergy and Clinical Immunology Unit; 🇮🇱 Tel Hashomer, Israel

Universita degli Studi di Napoli 'Federico II'; 🇮🇹 Napoli,, Italy

Derriford Combined Laboratory, Department of Clinical Immunology & Allergy; 🇬🇧 Plymouth, United Kingdom

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Barts & The London NHS Trust, Pathology and Pharmacy Building; 🇬🇧 London, United Kingdom

Hopital Europeen Georges Pompidou Immunologie Clinique; 🇫🇷 Paris, Paris Cedex 15, France

Klinkum der Johann Wolfgang Goethe-Universitat; 🇩🇪 Frankfurt am Main, Germany

Universitäts-Hals-Nasen-Ohren-Klinik Essen, Universität Duisburg-Essen; 🇩🇪 Essen, Germany

Universitätsspital Zürich / Dermatologische Klinik; 🇨🇭 Zurich, Switzerland

Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie, Charité; 🇩🇪 Berlin, Germany