Clinical trial NCT00912093: A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3)
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)
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
First posted: 2009-06-03
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient
timeFrame: Up to 120 hours post-dose
Secondary outcomes:
measure: Time to Onset of Primary Symptom Relief
timeFrame: Up to 120 hours post-dose
measure: Time to Almost Complete Symptom Relief
timeFrame: Up to 120 Hours post treatment
measure: Time to Subject-Assessed Initial Symptom Improvement
timeFrame: Up to 120 hours post-dose
measure: Time to Investigator-Assessed Initial Symptom Improvement
timeFrame: Up to 120 hours post-dose
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: Primary Care Associates of Alabaster
state: Alabama
city: Birmingham
country: United States
facility: UAB Lung Health Center
state: Alabama
city: Scottsdale
country: United States
facility: Medical Research of AZ A Division of Allergy & Immunology Assoc
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Allergy & Asthma Clinic, PA
state: Arkansas
city: Granada Hills
country: United States
facility: Allergy and Asthma Insititute of the Valley
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA - Clinical Immunology & Allergy
state: California
city: Stanford
country: United States
facility: Speciality Medical Clinic & Research Center
state: California
city: Stanford
country: United States
facility: Standford University
state: California
city: Colorado Springs
country: United States
facility: Asthma & Allergy Associates, PC
state: Colorado
city: Melbourne
country: United States
facility: Medical Associates of Brevard
state: Florida
city: Tampa
country: United States
facility: University of South Florida Division of Allergy and Immunology
state: Florida
city: Atlanta
country: United States
facility: Family Allergy and Asthma Center, PC
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evansville
country: United States
facility: Research Institute of Deaconess Clinic
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Asthma Center/ Hospitals & Clinics
state: Iowa
city: Shreveport
country: United States
facility: LSUHSC Allergy & Immunology
state: Louisiana
city: Chevy Chase
country: United States
facility: Institute for Asthman & Allergy, P.C.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: The Asthma Center
state: Missouri
city: Reno
country: United States
facility: University of Reno Nevada School of Medicine
state: Nevada
city: Edison
country: United States
facility: STARx Research Center, LLC
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center/Albert Einstein College of Medicine
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital Clinical Trials Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Asheville
country: United States
facility: Allergy Partners of Western North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Division of Immunology/Allergy
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Allergy Clinic
state: Oklahoma
city: Lake Oswego
country: United States
facility: Baker Allergy, Asthma & Dermatology Research Center LLC
state: Oregon
city: Bethlehem
country: United States
facility: Valley Clinical Research Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh (of UMPC)
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch (UTMB)
state: Texas
city: Houston
country: United States
facility: Texas A&M Health Science Center College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Allergy and Asthma Research Center, P.A.
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Garran
country: Australia
facility: Canberra Hospital Department of Immunology
state: Australian Capital Territory
city: Campbelltown
country: Australia
facility: Dept of Medicine Immunology & Allergy Campbelltown Hospital
state: New South Wales
city: Parkville
country: Australia
facility: Royal Melbourne Hospital Department of Immunology
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Edmonton
country: Canada
facility: NACTRC
state: Alberta
city: Ottawa
country: Canada
facility: Allergy & Asthma Research Centre
state: Ontario
city: Quebec City
country: Canada
facility: Centre de recherché Appliquée en allergie de Québec
state: Quebec
city: Budapest
country: Hungary
facility: 3rd Department of Internal Medicine Semmelweis University
city: Haifa
country: Israel
facility: Bnai-Zion Medical Center Division of Immunology & Allergy
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean Mures Sectia Medicina Interna
state: Transylvania
city: St Petersburg
country: Russian Federation
facility: Medical Academy of Postgraduate Education
state: Saint Petersburg
city: St Petersburg
country: Russian Federation
facility: Autonomous Non Commercial Organization
state: Saint Petersburg
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of City of Moscow
city: Moscow
country: Russian Federation
facility: State Enterprise State Scientific Centre
city: Moscow
country: Russian Federation
facility: State Educational Institution of Additional Profess. Edu. Moscow
city: Smolensk
country: Russian Federation
facility: Municipal Medical & Preventive Treatment Institution
city: Vladivostok
country: Russian Federation
facility: Regional Clinical Center of Specialized Medical Treatment
city: Cape Town
country: South Africa
facility: Allergy Diagnostic and Clinical Research Unit (ADCRU)
state: Mowbray
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk national Medical University
city: Kyiv
country: Ukraine
facility: National Medical Academy for Postgraduate Education
city: Kyiv
country: Ukraine
facility: Institute of Otolaryngology
city: Poltava
country: Ukraine
facility: Ukranian Medical Stomatological Academy Dept of Int Diseases
city: Vinnitsa
country: Ukraine
facility: Vinnitsa Medical Academy Chair of Internal Disease
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Lumry WR, Farkas H, Moldovan D, Toubi E, Baptista J, Craig T, Riedl M. Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. Int Arch Allergy Immunol. 2015;168(1):44-55. doi: 10.1159/000441060. Epub 2015 Nov 11.
citation: Maurer M, Longhurst HJ, Fabien V, Li HH, Lumry WR. Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting. Allergy Asthma Proc. 2014 Sep-Oct;35(5):377-81. doi: 10.2500/aap.2014.35.3780. Epub 2014 Aug 6.
citation: Bas M. Clinical efficacy of icatibant in the treatment of acute hereditary angioedema during the FAST-3 trial. Expert Rev Clin Immunol. 2012 Nov;8(8):707-17. doi: 10.1586/eci.12.67.
citation: Lumry WR, Li HH, Levy RJ, Potter PC, Farkas H, Moldovan D, Riedl M, Li H, Craig T, Bloom BJ, Reshef A. Randomized placebo-controlled trial of the bradykinin B(2) receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011 Dec;107(6):529-37. doi: 10.1016/j.anai.2011.08.015. Epub 2011 Oct 5.