title: EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema.
abstract: 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.
  
  
  CONCLUSIONS
  Ecallantide appears to be an effective and safe treatment for acute attacks of HAE.
authors.affiliation: Family Allergy & Asthma Center PC, Atlanta, Georgia 30342, USA. levyr@familyallergycenter.com
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Levy
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.forename: Donald L
authors.initials: DL
authors.lastname: McNeil
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.forename: Marilyn
authors.initials: M
authors.lastname: Campion
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Horn
authors.forename: William E
authors.initials: WE
authors.lastname: Pullman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D010455:Peptides; C511194:ecallantide