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

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 \[100\] to significant worsening \[-100\]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.

Time frame: 4 hours post-dose (DOUBLE-BLIND PART)

Population: ITT as treated: two patients randomized on the same day at the same study center were administered treatment opposite to their randomized treatment assignment. Data were analyzed based on actual treatment received. Imputation was used to account for emerging symptoms and medical intervention. Best possible score = 100; worst possible score = -100.

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 (minimally important difference) was indicated by a reduction in the score of 0.30 or more.

Time frame: baseline, 4 hours post-dose (DOUBLE-BLIND PART)

Population: ITT as treated: two patients randomized on the same day at the same center were administered treatment opposite to their randomized treatment assignments. Data were analyzed based on their actual treatment received. Imputation was used to account for emerging symptoms and medical intervention. Best possible score = 0.0; worst possible score = 3.0.

The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline. Patients were asked overall how are you feeling compared to how they felt before study drug. Answer options were a lot worse, a little worse, same, a little better or a lot better or resolved. Significant improvement was the first time that the patient responded to the assessment as a little better or resolved.

Time frame: 4 hours post-dose (DOUBLE-BLIND PART)

Population: ITT as treated. Patients not reporting significant improvement before 4 hours were censored at 4 hours. Patients receiving additional HAE therapy within 4 hours were censored at the time of the medical intervention. The time to significant improvement is not provided in this display as the median time for placebo was not reached by 4 hours.

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 (REPEAT-DOSING PART)

Population: Treatment episode 1 contains data only from those participants who were new patients in the repeat-dosing part. Treatment episode 2 and beyond contain data pooled from patients treated in the double-blind part (ecallantide or placebo) and the repeat-dosing part. Data imputation was used to account for emerging symptoms and medical intervention.

Patient-reported severity of symptom complexes at baseline, by symptom complex and treatment group. Patients were to have at least one symptom complex that was moderate or severe. Patients could present with multiple symptom complexes, some of which could be mild. Mild=noticeable but do not impact daily living activities; Moderate=treatment or intervention is highly desirable and activities of daily living are impacted; Severe=require treatment or intervention due to inability to perform activities of daily living. The results are for number of patients with symptom complexes including mild, moderate and severe, provided the patients have at least one symptom complex that was moderate or severe

Time frame: Baseline

The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline (ie,immediately before treatment) using the following 5-category scale from significant improvement (Score = 100)to significant worsening (Score = -100)

Time frame: 4 hours post-dose (REPEAT-DOSING PART)

Population: Patients not reporting significant improvement before 4 hours were censored at 4 hours. Patients receiving additional HAE therapy within 4 hours were censored at the time of the medical intervention. The time to significant improvement is not provided in this display as the interquartile range (IQR) was not reached by 4 hours for most episodes.

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 \[100\] to significant worsening \[-100\]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.

Time frame: 4 hours post-dose (REPEAT-DOSING PART)

Population: Treatment episode 1 contains data only from those participants who were new patients in the repeat-dosing part. Treatment episode 2 and beyond contain data pooled from patients treated in the double-blind part (ecallantide or placebo) and the repeat-dosing part. Data imputation was used to account for emerging symptoms and medical intervention.