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

This study has been completed.
Sponsor:
Collaborator:
Jerini AG
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00997204
First received: October 16, 2009
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hereditary Angioedema
Drug: Icatibant
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant [ Time Frame: 7 days from the beginning of each phase ] [ Designated as safety issue: Yes ]

    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:
  • 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 [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 151
Study Start Date: September 2009
Study Completion Date: September 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Icatibant- Naive Treatment Phase
Single subcutaneous injection of icatibant, 30 mg
Drug: Icatibant
Single subcutaneous injection of icatibant, 30 mg
Other Name: Brand name, Firazyr®
Experimental: icatibant- Self administration Phase
Single subcutaneous injection of icatibant, 30 mg
Drug: Icatibant
Single subcutaneous injection of icatibant, 30 mg
Other Name: Brand name, Firazyr®

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00997204

Locations
Argentina
Hospital Britanico Unidad de Alergia
Buenos Aires, Argentina, C1035AAT
Austria
Universitätsklinik für Dermatologie und Venerologie
Graz, Austria, 8036
Denmark
Odense Universitetshospital-OUH
Odense, I og Alergicentret, Denmark
France
Centre Hospitalier Universitaire/ Service de Dermatologie
Angers, Angers Cedex 09, France, 49933
Hospital Edouaed Herriot
Lyon, Cedex 03, France, 69437
Clinique Universitaire de Medicine/ Centre National de reference
Grenoble, Grenoble Cedex 09, France, 38043
Hopital Claude Huriex/ Service de medicine interne
Lille, Lille Cedex, France, 59037
Hopital Europeen Georges Pompidou Immunologie Clinique
Paris, Paris Cedex 15, France, 75015
Germany
Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie, Charité
Berlin, Germany, 10117
Universitäts-Hals-Nasen-Ohren-Klinik Essen, Universität Duisburg-Essen
Essen, Germany, 45127
Klinkum der Johann Wolfgang Goethe-Universitat
Frankfurt am Main, Germany, 60590
Hautklinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität
Mainz, Germany, 55101
Israel
Bnai-Zion M.C. Clinical Immunology and Allergy Division
Haifa, Israel, 31048
Tel Aviv Sourasky Medical Center - Allergy Unit
Tel Aviv, Israel, 64239
The Chaim Sheba Medical Center, The Allergy and Clinical Immunology Unit
Tel Hashomer, Israel, 52621
Italy
Ospedale Luigi Sacco
Milano, Italy, 20157
Universita degli Studi di Napoli 'Federico II'
Napoli,, Italy, 80131
Spain
Hospital Universitario Vall de Hebrón / Sección de Alergia, Escola Infermeria
Barcelona, Spain, 08035
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Hospital Universitario La Paz, Servicio de Alergia
Madrid, Spain, 28046
Hospital Universitario La Fe, Servicio de Alergia
Valencia, Spain, 46009
Switzerland
Luzerner Kantonsspital
Luzern, Switzerland
Universitätsspital Zürich / Dermatologische Klinik
Zurich, Switzerland, 8091
United Kingdom
Southmead Hospital, Department of Immunology
Bristol, United Kingdom, BS10 5NB
Barts & The London NHS Trust, Pathology and Pharmacy Building
London, United Kingdom, E1 2ES
Derriford Combined Laboratory, Department of Clinical Immunology & Allergy
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Shire
Jerini AG
Investigators
Study Director: Anja D. Lachmann, Dr. Jerini AG
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00997204     History of Changes
Other Study ID Numbers: JE049-3101, 2008-000071-25
Study First Received: October 16, 2009
Results First Received: November 4, 2013
Last Updated: June 30, 2014
Health Authority: Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ethics Commission
Switzerland: Swissmedic
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Denmark: Danish Medicines Agency

Keywords provided by Shire:
HAE
Type I HAE
Type II HAE

Additional relevant MeSH terms:
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Icatibant
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 27, 2014