Clinical trial NCT00997204: EASSI - Evaluation of the Safety of Self-Administration With Icatibant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: HAE
Type I HAE
Type II HAE
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Jerini AG
First posted: 2009-10-19
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant
timeFrame: 7 days from the beginning of each phase
Secondary outcomes:
measure: 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
timeFrame: 48 hours post-dose
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Britanico Unidad de Alergia
city: Graz
country: Austria
facility: Universitätsklinik für Dermatologie und Venerologie
city: Odense
country: Denmark
facility: Odense Universitetshospital-OUH
state: I Og Alergicentret
city: Angers
country: France
facility: Centre Hospitalier Universitaire/ Service de Dermatologie
state: Angers Cedex 09
city: Lyon
country: France
facility: Hospital Edouaed Herriot
state: Cedex 03
city: Grenoble
country: France
facility: Clinique Universitaire de Medicine/ Centre National de reference
state: Grenoble Cedex 09
city: Lille
country: France
facility: Hopital Claude Huriex/ Service de medicine interne
state: Lille Cedex
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou Immunologie Clinique
state: Paris Cedex 15
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie, Charité
city: Essen
country: Germany
facility: Universitäts-Hals-Nasen-Ohren-Klinik Essen, Universität Duisburg-Essen
city: Frankfurt am Main
country: Germany
facility: Klinkum der Johann Wolfgang Goethe-Universitat
city: Mainz
country: Germany
facility: Hautklinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität
city: Haifa
country: Israel
facility: Bnai-Zion M.C. Clinical Immunology and Allergy Division
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center - Allergy Unit
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center, The Allergy and Clinical Immunology Unit
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Napoli,
country: Italy
facility: Universita degli Studi di Napoli 'Federico II'
city: Barcelona
country: Spain
facility: Hospital Universitario Vall de Hebrón / Sección de Alergia, Escola Infermeria
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Servicio de Alergia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe, Servicio de Alergia
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Zurich
country: Switzerland
facility: Universitätsspital Zürich / Dermatologische Klinik
city: Bristol
country: United Kingdom
facility: Southmead Hospital, Department of Immunology
city: London
country: United Kingdom
facility: Barts & The London NHS Trust, Pathology and Pharmacy Building
city: Plymouth
country: United Kingdom
facility: Derriford Combined Laboratory, Department of Clinical Immunology & Allergy
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Aberer W, Maurer M, Reshef A, Longhurst H, Kivity S, Bygum A, Caballero T, Bloom B, Nair N, Malbran A. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema. Allergy. 2014 Mar;69(3):305-14. doi: 10.1111/all.12303.