Safety and Efficacy Study of Repeated Doses of DX-88 (Ecallantide) to Treat 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 repeated doses of ecallantide in the treatment of acute attacks of hereditary angioedema and to allow HAE patients continued access to ecallantide. In addition, patients enrolled in DX-88/20 (EDEMA4) trial will be followed up and treated for subsequent attacks in this trial.

Detailed Description
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This is an open label trial. The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide in the treatment of acute attacks of hereditary angioedema. This study is designed to provide efficacy and safety data on repeated use of 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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Open-label Patient Continuation of DX-88 (Ecallantide) for Acute Hereditary Angioedema Attacks

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: 10 years of age or older Documented diagnosis of HAE (Type I or II) Willing and able to give informed consent Acute HAE attack at time of presentation Exclusion Criteria: Receipt of an investigational drug or device, within 30 days prior to study treatment, other than DX-88 (ecallantide) Pregnancy or breastfeeding Receipt of non-investigational C1-INH or DX-88 within 72 hours of treatment Patients eligible for current, ongoing clinical trial in which DX 88 (ecallantide) is offered

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DX-88 (ecallantide)<br>DX-88 (ecallantide) Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose. | Drug: ecallantide<br>* solution for SC injection, one 30 mg dose per HAE attack<br>* Other names: DX-88;|

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 Hrs Post Dosing | Mean Symptom Complex Severity (MSCS) score is a validated point-in-time measure of symptom severity. At baseline and 4 hrs, 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. | 4 hrs post dose after every episode | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | The Treatment Outcome Score (TOS)is a validated measure of response to therapy. Response assessment for each symptom complex (internal head/neck, stomach/GI, genital/buttocks, external head/neck or cutaneous) was to be weighted based on the severity of symptom complexes at baseline. Severity assessment at baseline was rated on a categorical scale (1=mild, 2=moderate, 3=severe) for symptoms at each affected symptom complex. Response assessment of each symptom complex post-dosing relative to baseline used a scale (100=significant improvement, 50=improvement, 0=same). The weighted values were used to calculate the composite TOS. A TOS greater than 0 denotes an improvement in symptoms compared with baseline severity. | 4 hrs post dose after every episode | 
| Time to Significant Improvement | Time to significant improvement in overall response based on the period from 15 minutes after dosing through 4 hrs post dosing. Significant improvement was defined as a response of a lot better or resolved in the overall response assessment. | 15 min - 4 hrs post dose after every episode |