Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)

The Mean Symptom Complex Severity (MSCS) score is a validated, comprehensive point-in-time measure of symptom severity. At baseline and 4 hours, patients rated the severity on a categorical scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more.

Time frame: baseline, 4 hours post-dose

Population: Patients were excluded from the analysis if they did not have data for the endpoint being analyzed. Reasons for patients being excluded are for ecallantide: 1 patient treated for severe upper airway compromise; for placebo: 3 patient treated for severe upper airway compromise and 3 patients with missing 4-hour data. Best score=0.0; worst score=3.0.

A successful response was defined as improvement in existing laryngeal symptom complex,stabilization of an existing peripheral symptom complex, or a change from baseline in the MSCS score at 4 hours of at least -1.0.

Time frame: baseline, 4 hours post-dosing

Population: Diary information was not available for 1 patient in the placebo arm. This patient was considered not evaluable and excluded from the analysis.

Patients were to be asked to perform an overall response assessment at intervals during the first 4 hours post-dose. Assessments were to be made relative to baseline (ie, immediately before initial dosing) using a 5-category scale. Categories were: significant improvement = a lot better or resolved; improvement = a little better; same = response unchanged; worsening = a little worse; significant worsening = a lot worse. Significant improvement is the first time that a patient responded to the overall response assessment as a lot better or resolved.

Time frame: 4 hours post-dose

Population: The time to significant improvement is not provided in this display as the estimated median times were not reached by 240 minutes. Instead, the number of patients with significant improvement is provided per treatment arm.

Maintenance of significant improvement was defined as achieving and maintaining a significant improvement in overall response through 24 hours after dosing. Patient response categories were: significant improvement = a lot better or resolved; improvement = a little better; same = response unchanged; worsening = a little worse; significant worsening = a lot worse.

Time frame: 24 hours post-dosing

Population: Diary information was not available for 1 patient in the placebo arm. This patient was considered not evaluable and excluded from the analysis.

Treatment Outcome Score (TOS) is a validated, comprehensive measure of symptom response to treatment. At 4 hours , patient assessment of response characterized by their change from baseline in symptom severity and collected by anatomic site of attack involvement, was recorded on a categorical scale (significant improvement \[100; best value\]to significant worsening \[-100; worst value\]). Clinically meaningful improvement was indicated by a TOS of 30 or higher.

Time frame: 4 hours post-dose

Population: Patients were excluded from this analysis if they did not have data for the endpoint being analyzed. The reasons for patients being excluded from this analysis are for ecallantide: 1 patient treated for severe upper airway compromise and for placebo: 3 patient treated for severe upper airway compromise and 3 patients with missing 4-hour data.