EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema

• Published in: Annals of allergy, asthma, & immunology Vol. 104; no. 6; pp. 523 - 529
• Main Authors: Levy, Robyn J., MD, Lumry, William R., MD, McNeil, Donald L., MD, Li, H. Henry, MD, PhD, Campion, Marilyn, MS, Horn, Patrick T., MD, PhD, Pullman, William E., BMedSc, MBBS, PhD, FRACP
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-2010; Elsevier
• Subjects: Acute Disease; Adolescent; Adult; Aged; Allergic diseases; Allergy and Immunology; Angioedemas, Hereditary - drug therapy; Biological and medical sciences; Dermatology; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Injections, Subcutaneous; Male; Medical sciences; Middle Aged; Peptides - administration & dosage; Peptides - adverse effects; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Phase III trial; Allergy; Immunopathology; Skin disease; Dermatology; Ecallantide; Subcutaneous; Acute; Hereditary; Angioneurotic edema; Immunology; Treatment; Double blind study
• DOI: 10.1016/j.anai.2010.04.012
• EISSN: 1534-4436
• ISSN: 1081-1206

Background Hereditary angioedema (HAE) is a genetic disorder resulting from low levels of C1-inhibitor activity that manifests as acute attacks of variable and sometimes life-threatening edema. Ecallantide is a novel potent inhibitor of human plasma kallikrein, a key mediator of the excessive formation of bradykinin associated with the signs and symptoms of an HAE attack. Objective To evaluate the efficacy and safety of ecallantide in the treatment of acute HAE attacks. Methods In this double-blind, placebo-controlled study, patients with a moderate to severe HAE attack were randomized 1:1 to receive 30 mg of subcutaneous ecallantide or placebo. The primary efficacy end point was change from baseline in mean symptom complex severity score 4 hours after dosing. Additional end points included treatment outcome score 4 hours after dosing and maintenance of significant overall improvement through 24 hours. Results Ninety-six patients were enrolled. Mean (SD) change from baseline in mean symptom complex severity score 4 hours after dosing was significantly greater with ecallantide use (−0.8 [0.6]) compared with placebo use (−0.4 [0.8]) ( P = .01 comparing distributions). Ecallantide therapy was also associated with a significantly larger mean (SD) treatment outcome score 4 hours after dosing vs placebo use (ecallantide: 53.4 [49.7]; placebo: 8.1 [63.2]; P = .003 comparing distributions). The benefit of ecallantide was apparent within 2 hours after dosing and was maintained through 24 hours after dosing. The safety profile was similar between the treatment groups. Conclusion Ecallantide appears to be an effective and safe treatment for acute attacks of HAE.