A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3)

Hereditary Angioedema Clinical Trial

Official title:

A Phase III Randomized, Double-Blind,Placebo-Controlled, Multicenter Study of Icatibant for Subcutaneous Injection in Patients With Acute Attacks of Hereditary Angioedema (HAE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00912093
• Other study ID #: HGT-FIR-054
• Secondary ID: 2009-015606-19
• Status: Completed
• Phase: Phase 3
• Start date: July 16, 2009
• Est. completion date: October 1, 2010

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to evaluate the efficacy and safety of icatibant compared to placebo in patients experiencing acute attacks of hereditary angioedema (HAE).

Description:

This Phase III study consisted of two parts: A controlled phase and an open label extension (OLE) phase.

The controlled phase describes the double blind part of the study and was intended to evaluate the efficacy and safety of icatibant compared with placebo for the first treated cutaneous and/or abdominal attack.

Patients with moderate to severe abdominal or cutaneous attacks were randomized to receive a single, blinded, subcutaneous injection of icatibant (30 mg) or placebo. After a protocol amendment, patients with mild to moderate laryngeal HAE attacks were also randomized to receive a single, blinded subcutaneous injection of icatibant (30 mg) or placebo in order to obtain blinded, controlled efficacy and safety data for this subset of subjects. Patients experiencing severe laryngeal attacks (post-amendment) or mild to severe laryngeal attacks (pre-amendment) were to receive open-label icatibant.

After treatment of the first attack in the controlled phase, patients were eligible to enter the OLE phase. In the OLE phase, patients who experienced angioedema attacks severe enough to warrant treatment were to be treated with s.c. icatibant as appropriate until the study was discontinued or the product was commercially available.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: October 1, 2010
• Est. primary completion date: October 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

1. The patient is =18 years old at the time of informed consent.

2. The patient has a documented diagnosis of HAE type I or II. The diagnosis will be confirmed either by documented decreased C4 levels and/or immunogenic or functional C1-INH deficiency results (<50% of normal levels) consistent with HAE types I and II or by medical history.

3. The current HAE attack must be in the cutaneous, abdominal and/or laryngeal (inclusive of laryngeal and pharyngeal) areas.

4. Cutaneous or abdominal HAE attacks must be moderate to very severe as determined by investigator global assessment at pre-treatment assessments

5. The patient must report at least 1 VAS score = 30mm

6. The patient commences treatment within 6 hours of the attack becoming at least mild (laryngeal) or moderate (non-laryngeal) in severity, but not more than 12 hours after the onset of the attack.

7. Women of childbearing potential must have a negative urine pregnancy test and must use appropriate methods to prevent pregnancy during their participation in the study.

Exclusion Criteria:

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

1. The patient has a diagnosis of angioedema other than HAE type I or II.

2. The patient has received previous treatment with icatibant.

3. The patient has participated in a clinical trial and has received treatment with another investigational medicinal product within the past 30 days.

4. The patient has received treatment with any pain medication since the onset of the current angioedema attack.

5. The patient has received replacement therapy (fresh frozen plasma [FFP], C1-INH products) less than 5 days (120 hours) from the onset of the current angioedema attack.

6. The patient is receiving treatment with angiotensin converting enzyme (ACE) inhibitors.

7. Evidence of coronary artery disease based on medical history or screening examination in particular unstable angina pectoris or severe coronary heart disease;

8. The patient has a serious concomitant illness or condition that, in the opinion of the Investigator, would be a contraindication for participation in the trial.

9. The patient is pregnant or breastfeeding.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• Icatibant
Single subcutaneous injection of icatibant, 30 mg
• Placebo
Single subcutaneous injection of matching placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Dept of Medicine Immunology & Allergy Campbelltown Hospital	Campbelltown	New South Wales
Australia	Canberra Hospital Department of Immunology	Garran	Australian Capital Territory
Australia	Royal Melbourne Hospital Department of Immunology	Parkville	Victoria
Canada	NACTRC	Edmonton	Alberta
Canada	Allergy & Asthma Research Centre	Ottawa	Ontario
Canada	Centre de recherché Appliquée en allergie de Québec	Quebec City	Quebec
Hungary	3rd Department of Internal Medicine Semmelweis University	Budapest
Israel	Bnai-Zion Medical Center Division of Immunology & Allergy	Haifa
Israel	Tel Aviv Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Romania	Spitalul Clinic Judetean Mures Sectia Medicina Interna	Targu Mures	Transylvania
Russian Federation	State Educational Institution of Additional Profess. Edu. Moscow	Moscow
Russian Federation	State Enterprise State Scientific Centre	Moscow
Russian Federation	State Healthcare Institution of City of Moscow	Moscow
Russian Federation	Municipal Medical & Preventive Treatment Institution	Smolensk
Russian Federation	Autonomous Non Commercial Organization	St Petersburg	Saint Petersburg
Russian Federation	Medical Academy of Postgraduate Education	St Petersburg	Saint Petersburg
Russian Federation	Regional Clinical Center of Specialized Medical Treatment	Vladivostok
South Africa	Allergy Diagnostic and Clinical Research Unit (ADCRU)	Cape Town	Mowbray
Ukraine	Ivano-Frankivsk national Medical University	Ivano-Frankivsk
Ukraine	Institute of Otolaryngology	Kyiv
Ukraine	National Medical Academy for Postgraduate Education	Kyiv
Ukraine	Ukranian Medical Stomatological Academy Dept of Int Diseases	Poltava
Ukraine	Vinnitsa Medical Academy Chair of Internal Disease	Vinnitsa
United States	Primary Care Associates of Alabaster	Alabaster	Alabama
United States	Allergy Partners of Western North Carolina	Asheville	North Carolina
United States	Family Allergy and Asthma Center, PC	Atlanta	Georgia
United States	Valley Clinical Research Center	Bethlehem	Pennsylvania
United States	UAB Lung Health Center	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center/Albert Einstein College of Medicine	Bronx	New York
United States	Institute for Asthman & Allergy, P.C.	Chevy Chase	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati Division of Immunology/Allergy	Cincinnati	Ohio
United States	Asthma & Allergy Associates, PC	Colorado Springs	Colorado
United States	Optimed Research, LTD	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	STARx Research Center, LLC	Edison	New Jersey
United States	Research Institute of Deaconess Clinic	Evansville	Indiana
United States	University of Texas Medical Branch (UTMB)	Galveston	Texas
United States	Allergy and Asthma Insititute of the Valley	Granada Hills	California
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Texas A&M Health Science Center College of Medicine	Houston	Texas
United States	University of Iowa Asthma Center/ Hospitals & Clinics	Iowa City	Iowa
United States	University of California San Diego	La Jolla	California
United States	Baker Allergy, Asthma & Dermatology Research Center LLC	Lake Oswego	Oregon
United States	Little Rock Allergy & Asthma Clinic, PA	Little Rock	Arkansas
United States	UCLA - Clinical Immunology & Allergy	Los Angeles	California
United States	Medical Associates of Brevard	Melbourne	Florida
United States	Winthrop University Hospital Clinical Trials Center	Mineola	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Children's Hospital of Pittsburgh (of UMPC)	Pittsburgh	Pennsylvania
United States	University of Reno Nevada School of Medicine	Reno	Nevada
United States	The Asthma Center	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Allergy and Asthma Research Center, P.A.	San Antonio	Texas
United States	Medical Research of AZ A Division of Allergy & Immunology Assoc	Scottsdale	Arizona
United States	LSUHSC Allergy & Immunology	Shreveport	Louisiana
United States	Speciality Medical Clinic & Research Center	Stanford	California
United States	Standford University	Stanford	California
United States	University of South Florida Division of Allergy and Immunology	Tampa	Florida
United States	Tulsa Allergy Clinic	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  Israel,  Romania,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient	Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time.	Up to 120 hours post-dose
Secondary	Time to Onset of Primary Symptom Relief	Time to primary symptom relief was calculated from the time of study drug administration to the onset of primary symptom relief, where onset of primary symptom relief was determined using the subject-assessed VAS score for a single primary symptom (determined by edema location) and defined as the earliest of 3 consecutive non-missing measurements in which a pre-specified reduction from the pretreatment value was met. Subjects who did not achieve primary symptom relief within the observation period were censored at the last observation time.	Up to 120 hours post-dose
Secondary	Time to Almost Complete Symptom Relief	Time to almost complete symptom relief was calculated from the time of study drug administration to almost complete symptom relief, where almost complete symptom relief was defined as the earliest of 3 consecutive non-missing measurements in which all VAS scores <10 mm. Subjects who did not achieve almost complete symptom relief within the observation period were censored at the last observation time.	Up to 120 Hours post treatment
Secondary	Time to Subject-Assessed Initial Symptom Improvement	Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the subject as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.	Up to 120 hours post-dose
Secondary	Time to Investigator-Assessed Initial Symptom Improvement	Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the investigator as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.	Up to 120 hours post-dose