Hereditary AngioedemaPhase 3EASSINCT00997204
EASSI - Evaluation of the Safety of Self-Administration With Icatibant
A Phase 3 study testing Icatibant in people with Hereditary Angioedema, run by Shire at 26 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- Icatibant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 26 sitesin 10 countries
- Study dates
- 25 Sep 2009to 22 Jun 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet the following criteria to be enrolled in this study.
- Males and females 18 years of age at the time of informed consent
- 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
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- 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.
- Mental and physical condition allowing patients to complete baseline assessment, to self-administer icatibant and to follow other study procedures.
- Ability to provide signed written informed consent after all aspects of the study have been explained and discussed with the patient.
Who cannot join
- Patients who meet any of the following criteria will be excluded from the study.
- Participation in a clinical trial of another investigational medicinal product within the past month (except a previous icatibant study).
- Diagnosis of angioedema other than Type I or Type II HAE.
- Evidence of symptomatic coronary artery disease based on medical history, in particular, unstable angina pectoris or severe coronary heart disease.
- Congestive heart failure (NYHA Class 3 and 4).
- Stroke within the past 6 months.
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- Treatment with angiotensin converting enzyme (ACE) inhibitor.
- Pregnancy and/or breast-feeding.
- In the opinion of the investigator: mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study.
- 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.
- In the opinion of the investigator: inability to manage study medication or self-administration of an injection.
Trial locations and contacts
26 sites in 10 countries.
26 sites in 10 countries
France5 sites
Centre Hospitalier Universitaire/ Service de Dermatologie
Angers, Angers Cedex 09, 49933
Clinique Universitaire de Medicine/ Centre National de reference
Grenoble, Grenoble Cedex 09, 38043
Hopital Claude Huriex/ Service de medicine interne
Lille, Lille Cedex, 59037
Hospital Edouaed Herriot
Lyon, Cedex 03, 69437
Hopital Europeen Georges Pompidou Immunologie Clinique
Paris, Paris Cedex 15, 75015
Germany4 sites
Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie, Charité
Berlin, 10117
Universitäts-Hals-Nasen-Ohren-Klinik Essen, Universität Duisburg-Essen
Essen, 45127
Klinkum der Johann Wolfgang Goethe-Universitat
Frankfurt am Main, 60590
Hautklinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität
Mainz, 55101
Spain4 sites
Hospital Universitario Vall de Hebrón / Sección de Alergia, Escola Infermeria
Barcelona, 08035
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario La Paz, Servicio de Alergia
Madrid, 28046
Hospital Universitario La Fe, Servicio de Alergia
Valencia, 46009
Israel3 sites
Bnai-Zion M.C. Clinical Immunology and Allergy Division
Haifa, 31048
Tel Aviv Sourasky Medical Center - Allergy Unit
Tel Aviv, 64239
The Chaim Sheba Medical Center, The Allergy and Clinical Immunology Unit
Tel HaShomer, 52621
United Kingdom3 sites
Southmead Hospital, Department of Immunology
Bristol, BS10 5NB
Barts & The London NHS Trust, Pathology and Pharmacy Building
London, E1 2ES
Derriford Combined Laboratory, Department of Clinical Immunology & Allergy
Plymouth, PL6 8DH
Italy2 sites
Ospedale Luigi Sacco
Milan, 20157
Universita degli Studi di Napoli 'Federico II'
Naples, 80131
Switzerland2 sites
Luzerner Kantonsspital
Lucerne
Universitätsspital Zürich / Dermatologische Klinik
Zurich, 8091
About this study
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
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.
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- Icatibant
- Keywords
- HAE, Type I HAE, Type II HAE
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IcatibantDrug
Also called Brand name, Firazyr®
Single subcutaneous injection of icatibant, 30 mg
| Study group | Role | What they receive |
|---|---|---|
| Icatibant- Naive Treatment Phase | Experimental | Single subcutaneous injection of icatibant, 30 mg Receives: Drug: Icatibant |
| icatibant- Self administration Phase | Experimental | Single subcutaneous injection of icatibant, 30 mg Receives: Drug: Icatibant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant
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.
Measured: 7 days from the beginning of each phase
Secondary outcomes (1)
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
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.
Measured: 48 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2009 (estimated)
- Study start25 Sep 2009
- Primary completion22 Jun 2011
- Study completion22 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Jerini AG
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00997204
- Sponsor's protocol ID
- JE049-3101
- Other IDs
- 2008-000071-25, 2008
- Acronym
- EASSI
- Status last verified
- May 2021
- First submitted
- 16 Oct 2009
- Last updated
- 11 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24438203
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00997204
- Acronym / sponsor ID
- EASSI / JE049-3101
- Conditions
- Hereditary Angioedema
- Keywords
- HAE, Type I HAE, Type II HAE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- Jerini AG
- Study start
- 25 Sep 2009 (actual)
- Primary completion
- 22 Jun 2011 (actual)
- Study completion
- 22 Jun 2011 (actual)
- First posted
- 19 Oct 2009 (estimated)
- Results
- Posted 28 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Icatibant- Naive Treatment Phase | Experimental | Drug: IcatibantSingle subcutaneous injection of icatibant, 30 mg |
| icatibant- Self administration Phase | Experimental | Drug: IcatibantSingle subcutaneous injection of icatibant, 30 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Each patient must meet the following criteria to be enrolled in this study.
- Males and females 18 years of age at the time of informed consent
- Documented diagnosis of HAE Type I or II based on ALL of the following criteria:
- 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.
- Mental and physical condition allowing patients to complete baseline assessment, to self-administer icatibant and to follow other study procedures.
Key exclusion criteria (11 listed)
- Patients who meet any of the following criteria will be excluded from the study.
- Participation in a clinical trial of another investigational medicinal product within the past month (except a previous icatibant study).
- Diagnosis of angioedema other than Type I or Type II HAE.
- Evidence of symptomatic coronary artery disease based on medical history, in particular, unstable angina pectoris or severe coronary heart disease.
- Congestive heart failure (NYHA Class 3 and 4).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IcatibantAlso: Brand name, Firazyr®Single subcutaneous injection of icatibant, 30 mg | Drug | Icatibant- Naive Treatment Phase, icatibant- Self administration Phase |
Primary outcome
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
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24438203Aberer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
26 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Icatibant in people with Hereditary Angioedema, run by Shire at 26 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in France, Germany, Spain, Israel, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00997204, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021.