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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of DX-88 (ecallantide) versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema.

Detailed Description
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This is a randomized placebo-controlled trial. The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema. This study is conducted under Special Protocol Assessment with the FDA and is designed to provide pivotal efficacy data on ecallantide. These data are intended to support the marketing authorization of ecallantide in the treatment of acute attacks of hereditary angioedema. Efficacy and safety of ecallantide will be evaluated in this study.

Official Title
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EDEMA4: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of DX-88 (Ecallantide) for the Treatment of Acute Attacks of Hereditary Angioedema

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Drug: ecallantide
* Drug: Phosphate Buffer Saline (PBS), pH 7.0


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 10 years of age or older Executed informed consent Documented diagnosis of HAE (Type I or II) Presentation at the site within 8 hours of patient recognition of an moderate to severe HAE acute attack Exclusion Criteria: Receipt of an investigational drug or device, within 30 days prior to study treatment Receipt of non-investigational C1-INH within 7 days of treatment Receipt of DX-88 (ecallantide) within 3 days prior to study treatment Diagnosis of acquired angioedema (AAE), estrogen-dependent angioedema or drug-induced angioedema (including angiotensin-converting enzyme inhibitor induced angioedema) Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 10 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DX-88 (ecallantide)<br>DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections. | Drug: ecallantide<br>* dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.<br>* Other names: DX-88;|
| Placebo Comparator: Placebo<br>Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections. | Drug: Phosphate Buffer Saline (PBS), pH 7.0<br>* given as three 1mL subcutaneous injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose | 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. | baseline, 4 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Outcome Score at 4 Hours Post-Dose | 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. | 4 hours post-dose | 
| Patients With Significant Improvement in Overall Response | 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. | 4 hours post-dose | 
| Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score | 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. | baseline, 4 hours post-dosing | 
| Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours | 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. | 24 hours post-dosing |