Observational Safety Study for KALBITOR (Ecallantide) in the Treatment of Acute Attacks of Hereditary Angioedema

A Phase 4, Long-Term Observational Safety Study to Evaluate Immunogenicity and Hypersensitivity With Exposure to KALBITOR (Ecallantide) for the Treatment of Acute Attacks of HAE

The objective of this study is to evaluate the formation of antibodies, the occurence of allergic reactions, and the risk of hypercoagulability and hypocoagulability in patients treated with KALBITOR (ecallantide).

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: ecallantide

Detailed Description

The objective of this study is to evaluate immunogenicity and hypersensitivity upon exposure to KALBITOR, in particular:

1. Determine the rate of anaphylaxis and Type I hypersensitivity reactions upon exposure to KALBITOR.
2. Determine the rate of seroconversion to anti-ecallantide antibodies upon exposure to KALBITOR.
3. Determine the rate of adverse events related to disordered coagulation (hypercoagulability and hypocoagulability) upon exposure to KALBITOR.

• Study Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Allergry and Asthma Clinical Research Center
  • California
    • Bell Gardens, California, United States, 90201
      • Sunrise Clinical Research
    • Granada Hills, California, United States, 91344
      • Allergy & Asthma Institute of the Valley
    • Los Angeles, California, United States, 90095-1680
      • Unidversity of California, Los Angeles David Geffen School of Medicine
    • Orange, California, United States, 92868
      • 705 West LaVeta
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research Inc.
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Center for Allergy, Asthma & Immunology
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida Asthma
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Brookstone Clinical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergry and Immunology
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic Downtown
    • Muncie, Indiana, United States, 47304
      • Muncie Allergy Ctr
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Allergy and Asthma Associates
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Ochsner Health System - Allergy, Asthma and Immunology Department
    • Metairie, Louisiana, United States, 70006
      • Clinical Research Specialists
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma and Allergy, P.C.
  • Massachusetts
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan Health System Allergy Specialty Clinic
    • Clinton Township, Michigan, United States, 48038
      • Asthma and Allergy Institute of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University School of Medicine
  • Nevada
    • Reno, Nevada, United States, 89503
      • University of Nevada School of Medicine - Department of Pediatrics
  • New Jersey
    • Iselin, New Jersey, United States, 08830
      • Allergy Treatment Center of New Jersey
  • New York
    • Bronx, New York, United States, 10465
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • North Syracuse, New York, United States, 13212
      • Medical Research Associates of CNY
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Allergy Partners of Western North Carolina
    • Sanford, North Carolina, United States, 27330
      • Specialty Medical Clinic and Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0563
      • Department of Internal Medicine, University of Cincinnati -MSB
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD
    • Toledo, Ohio, United States, 43615
      • Reynolds Clinic
    • Toledo, Ohio, United States, 43617
      • Toledo Institute of Clinical Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Allergy Clinic of the Tulsa, Inc.
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State University - Penn State Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah, Department of Dermatology
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Virginia Beach, Virginia, United States, 23452
  • Washington
    • Tacoma, Washington, United States, 98405
      • Puget Sound Allergy, Asthma and Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with hereditary angioedema, either naive or non-naive to KALBITOR (ecallantide) prior to enrollment in the study

Description

Inclusion Criteria:

• Patients indicated per the approved product label for KALBITOR
• Patient or guardian is able to understand and sign the informed consent form
• Patient is willing and able to undergo a skin test procedure at screening (baseline)

Exclusion Criteria:

• Patient contraindicated per the approved product label for KALBITOR
• Patient confirmed pregnancy or active breastfeeding
• Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients naive to KALBITOR; HAE patients that have not been treated with KALBITOR (ecallantide) prior to enrollment in the study	Drug: ecallantide; 30 mg SC; Other Names: Kalbitor
Patients non- naive to KALBITOR; HAE patients that have been treated with KALBITOR prior to enrollment in the study	Drug: ecallantide; 30 mg SC; Other Names: Kalbitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Anaphylaxis or Other Adverse Events Suggestive of Hypersensitivity	Based on medical review of multiple preferred terms for treatment emergent adverse events (TEAEs) suggestive of Type 1 hypersensitivity; terms included adverse drug reaction, anaphylaxis, anaphylactic reaction, anaphylactoid reaction, hypersensitivity, erythema, flushing, hot flush, pharyngeal edema, laryngeal edema, pruritus, pruritus generalized, rash, rash erythematous, rhinitis allergic, rhinorrhea, throat irritation, urticaria, urticaria localized, dyspnea, and wheezing. Records of patients with any of these TEAE referred terms were reviewed further to assess potential hypersensitivity reactions, considering factors such as timing of TEAEs in relationship to dose (ie, occurred within 24 hours after start of KALBITOR treatment), accompanying symptoms, Investigator causality assessment (ie, reported as possibly, probably, or definitely related to study drug), and any other available clinical information. Anaphylaxis subset determined based on criteria established by the NIAID.	12 months after first treatment
Occurrence of Seroconversion to Anti-ecallantide Antibodies Upon Exposure to KALBITOR.	Seroconversion is the development of detectable specific antibodies in the blood serum. Serum was tested for development of antibodies (irrespective of immunoglobulin class) against ecallantide at screening and at all safety evaluations. Positive results were to undergo a confirmatory test. Confirmed positive samples were further titered. Patients who developed an antibody response were evaluated for the development of neutralizing antibodies. Patients also had their serum analyzed for IgE-specific antibodies to ecallantide at screening and during safety evaluations. Positive results underwent a confirmatory test. Confirmed positive samples were further titered.	12 months after first treatment
Occurrence of Adverse Events Related to Disordered Coagulation (Hypercoagulability and Hypocoagulability) Upon Exposure to KALBITOR	Events of ecchymosis, hemorrhage, petechiae, spontaneous hemorrhage, hematoma, gastrointestinal bleeding, hemorrhagic stroke and any other term indicative of a bleeding event or increased tendency for bleeding were reviewed to determine the occurrence of hypocoagulability. Events of clotting, thrombosis, pulmonary embolism, vaso-occlusive stroke, myocardial infarction, and any other term indicative of a clotting event or increased risk of clotting were reviewed to determine the occurrence of hypercoagulability.	12 months after first treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Patient Response Assessment	The Overall Response Assessment was to be completed every 30 minutes after treatment until patient discharge. Patients evaluated their response to treatment as "a lot better or resolved," "a little better," "the same," "a little worse," or "a lot worse." The data presented is based on the best response achieved following a single dose of KALBITOR (Dose A) for the first HAE treatment episode. Responses of "a lot better or resolved" and "a little better" were combined to form a category of "Better." Similarly, "a little worse" and "a lot worse" were combined to form a category of "Worse." Patients treated in a clinic (study site) could have been discharged after an hour and hence may have only had 2 post-treatment evaluations (30 and 60 minutes); response assessments may not have been consistently provided when patients were treated at an alternate site outside of the study site.	within 4 hours post dose

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2010
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: HAE
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Ecallantide
• Other Study ID Numbers: DX-88/24