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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00912093
First received: June 2, 2009
Last updated: September 11, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Hereditary Angioedema
Drug: Icatibant
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient [ Time Frame: Up to 120 hours post-dose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Onset of Primary Symptom Relief [ Time Frame: Up to 120 hours post-dose ] [ Designated as safety issue: No ]
    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.

  • Time to Almost Complete Symptom Relief [ Time Frame: Up to 120 Hours post treatment ] [ Designated as safety issue: No ]
    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.

  • Time to Subject-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ] [ Designated as safety issue: No ]
    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.

  • Time to Investigator-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 98
Study Start Date: June 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Single subcutaneous injection of matching placebo
Drug: Placebo
Single subcutaneous injection of matching placebo
Experimental: Icatibant
Single subcutaneous injection of icatibant, 30 mg
Drug: Icatibant
Single subcutaneous injection of icatibant, 30 mg
Other Name: Firazyr

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

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. 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.
  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: NCT00912093

  Hide Study Locations
Locations
United States, Alabama
Primary Care Associates of Alabaster
Alabaster, Alabama, United States, 35007
UAB Lung Health Center
Birmingham, Alabama, United States, 35294
United States, Arizona
Medical Research of AZ A Division of Allergy & Immunology Assoc
Scottsdale, Arizona, United States, 85251
United States, Arkansas
Little Rock Allergy & Asthma Clinic, PA
Little Rock, Arkansas, United States, 72205
United States, California
Allergy and Asthma Insititute of the Valley
Granada Hills, California, United States, 91344
University of California San Diego
La Jolla, California, United States, 92093
UCLA - Clinical Immunology & Allergy
Los Angeles, California, United States, 90095
Speciality Medical Clinic & Research Center
Stanford, California, United States, 27330
Standford University
Stanford, California, United States, 94305
United States, Colorado
Asthma & Allergy Associates, PC
Colorado Springs, Colorado, United States, 80907
United States, Florida
Medical Associates of Brevard
Melbourne, Florida, United States, 32935
University of South Florida Division of Allergy and Immunology
Tampa, Florida, United States, 33613
United States, Georgia
Family Allergy and Asthma Center, PC
Atlanta, Georgia, United States, 30342
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
Research Institute of Deaconess Clinic
Evansville, Indiana, United States, 47713
United States, Iowa
University of Iowa Asthma Center/ Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Louisiana
LSUHSC Allergy & Immunology
Shreveport, Louisiana, United States, 71130
United States, Maryland
Institute for Asthman & Allergy, P.C.
Chevy Chase, Maryland, United States, 20815-6901
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
The Asthma Center
St. Louis, Missouri, United States, 63141
United States, Nevada
University of Reno Nevada School of Medicine
Reno, Nevada, United States, 89503
United States, New Jersey
STARx Research Center, LLC
Edison, New Jersey, United States, 08820
United States, New York
Montefiore Medical Center/Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Winthrop University Hospital Clinical Trials Center
Mineola, New York, United States, 11501
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, North Carolina
Allergy Partners of Western North Carolina
Asheville, North Carolina, United States, 28801
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati Division of Immunology/Allergy
Cincinnati, Ohio, United States, 45267
Optimed Research, LTD
Columbus, Ohio, United States, 43235
United States, Oklahoma
Tulsa Allergy Clinic
Tulsa, Oklahoma, United States, 74133
United States, Oregon
Baker Allergy, Asthma & Dermatology Research Center LLC
Lake Oswego, Oregon, United States, 97035
United States, Pennsylvania
Valley Clinical Research Center
Bethlehem, Pennsylvania, United States, 18020
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Pittsburgh (of UMPC)
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
AARA Research Center
Dallas, Texas, United States, 75231
University of Texas Medical Branch (UTMB)
Galveston, Texas, United States, 77555-0561
Texas A&M Health Science Center College of Medicine
Houston, Texas, United States, 77030
Allergy and Asthma Research Center, P.A.
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Australia, Australian Capital Territory
Canberra Hospital Department of Immunology
Woden, Australian Capital Territory, Australia
Australia, New South Wales
Dept of Medicine Immunology & Allergy Campbelltown Hospital
Campbelltown, New South Wales, Australia, 2560
Australia, Victoria
Royal Melbourne Hospital Department of Immunology
Parkville, Victoria, Australia, 3050
Australia
Royal Adelaide Hospital
Adelaide, Australia
Canada, Alberta
NACTRC
Edmonton, Alberta, Canada, T6G 2H7
Canada, Ontario
Allergy & Asthma Research Centre
Ottowa, Ontario, Canada, K1Y 4G2
Canada, Quebec
Centre de recherché Appliquée en allergie de Québec
Quebec City, Quebec, Canada, G1V 5M6
Hungary
3rd Department of Internal Medicine Semmelweis University
Budapest, Hungary, 1125
Israel
Bnai-Zion Medical Center Division of Immunology & Allergy
Haifa, Israel, 31048
Tel Aviv Medical Center
Tel Aviv, Israel, 64239
The Chaim Sheba Medical Center
Tel Hashomer, Israel, 52621
Romania
Spitalul Clinic Judetean Mures Sectia Medicina Interna
Tirgu Mures, Tigru-Mures, Romania, 540103
Russian Federation
State Healthcare Institution of City of Moscow
Moscow, Russian Federation, 115446
State Enterprise State Scientific Centre
Moscow, Russian Federation, 115478
State Educational Institution of Additional Profess. Edu. Moscow
Moscow, Russian Federation, 123182
Municipal Medical & Preventive Treatment Institution
Smolensk, Russian Federation, 214001
Medical Academy of Postgraduate Education
St Petersburg, Russian Federation, 194291
Autonomous Non Commercial Organization
St Petersburg, Russian Federation, 198216
Regional Clinical Center of Specialized Medical Treatment
Vladivostok, Russian Federation, 690091
South Africa
Allergy Diagnostic and Clinical Research Unit (ADCRU)
Cape Town, Mowbray, South Africa, 7700
Ukraine
Ivano-Frankivsk national Medical University
Ivano-Frankivsk, Ukraine, 76018
Institute of Otolaryngology
Kyiv, Ukraine, 03680
National Medical Academy for Postgraduate Education
Kyiv, Ukraine, 01133
Ukranian Medical Stomatological Academy Dept of Int Diseases
Poltava, Ukraine, 36039
Vinnitsa Medical Academy Chair of Internal Disease
Vinnitsa, Ukraine, 21029
Sponsors and Collaborators
Shire
Investigators
Study Director: Alan Kimura, M.D., PhD Shire
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00912093     History of Changes
Other Study ID Numbers: HGT-FIR-054, 2009-015606-19
Study First Received: June 2, 2009
Results First Received: July 11, 2014
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Ukraine: State Pharmacological Center - Ministry of Health

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

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

ClinicalTrials.gov processed this record on October 20, 2014