Efficacy and Safety Study of DX-88 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 determine if a subcutaneous dose of DX-88 (ecallantide; an investigational product) is safe and relieves symptoms of HAE in patients suffering from moderate to severe acute attacks of HAE.

Official Title
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A Double-blind, Placebo-controlled Study (72 Patients, Randomized 1:1) Followed by a Repeat-dosing Phase to Assess the Efficacy and Safety of DX-88 (Ecallantide; Recombinant Plasma Kallikrein Inhibitor) 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),


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10 and older Documented diagnosis of HAE, Type I or II Executed informed consent Presentation for treatment within 8 hours of patient recognition of moderate to severe HAE attack Exclusion Criteria: Receipt of investigational drug or device, other than DX-88, within 30 days of treatment Receipt of non-investigational C1-INH (C1 esterase inhibitor) within 7 days of treatment Diagnostic of acquired angioedema, estrogen-dependent angioedema or drug induced angioedema Pregnancy or breastfeeding Patients who have received DX-88 within 7 days of presentation for dosing in the Double-blind Phase

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>Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections. | Drug: Phosphate Buffer Saline (PBS),<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 |
| --- | --- | --- |
| 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] 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. | 4 hours post-dose (DOUBLE-BLIND PART) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose | 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. | baseline, 4 hours post-dose (DOUBLE-BLIND PART) | 
| Time to Significant Improvement in Overall Response | 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. | 4 hours post-dose (DOUBLE-BLIND PART) |