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

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.

Time frame: 12 months after first treatment

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.

Time frame: 12 months after first treatment

Population: Safety population; defined as all patients who received at least 1 treatment dose of 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.

Time frame: 12 months after first treatment

Population: Based on total number of patients who were not positive for the antibody class at study entry and had at least one post-baseline antibody evaluation. N=40 evaluable patients for all immunoglobulin antibody classes; N=41 evaluable patients for IgE to ecallantide antibodies; N=41 evaluable patients for neutralizing antibodies to ecallantide.

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.

Time frame: within 4 hours post dose

Population: Safety population; defined as all patients who received at least 1 treatment dose of KALBITOR. Analysis only includes episodes of patients who were treated at the study site.