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

Study Overview
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Brief Summary
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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).

Detailed Description
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The objective of this study is to evaluate immunogenicity and hypersensitivity upon exposure to KALBITOR, in particular: Determine the rate of anaphylaxis and Type I hypersensitivity reactions upon exposure to KALBITOR. Determine the rate of seroconversion to anti-ecallantide antibodies upon exposure to KALBITOR. Determine the rate of adverse events related to disordered coagulation (hypercoagulability and hypocoagulability) upon exposure to KALBITOR.

Official Title
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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

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Drug: ecallantide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients naive to KALBITOR<br>HAE patients that have not been treated with KALBITOR (ecallantide) prior to enrollment in the study | Drug: ecallantide<br>* 30 mg SC<br>* Other names: Kalbitor;|
| Patients non- naive to KALBITOR<br>HAE patients that have been treated with KALBITOR prior to enrollment in the study | Drug: ecallantide<br>* 30 mg SC<br>* Other names: Kalbitor;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE