Ecallantide for the treatment of acute attacks in hereditary angioedema

Marco Cicardi, Robyn J. Levy, Donald L. McNeil, Huamin Li, Albert L. Sheffer, Marilyn Campion, Patrick T. Horn, William E. Pullman

Research output: Contribution to journalArticle

Abstract

Background: Hereditary angioedema is a rare genetic disorder characterized by acute, intermittent, and potentially life-threatening attacks of edema of the skin and mucosa. We evaluated ecallantide, a newly developed recombinant plasma kallikrein inhibitor, for the treatment of acute attacks of angioedema. Methods: In this double-blind, placebo-controlled trial, patients with hereditary angioedema presenting with an acute attack were randomly assigned, in a 1:1 ratio, to receive subcutaneous ecallantide, at a dose of 30 mg, or placebo. Two measures of patient-reported outcomes were used to assess the response: treatment outcome scores, which range from +100 (designated in the protocol as significant improvement in symptoms) to -100 (significant worsening of symptoms), and the change from baseline in the mean symptom complex severity score, which range from +2 (representing a change from mild symptoms at baseline to severe symptoms after) to -3 (representing a change from severe symptoms at baseline to no symptoms after). The primary end point was the treatment outcome score 4 hours after study-drug administration. Secondary end points included the change from baseline in the mean symptom complex severity score at 4 hours and the time to significant improvement. Results: A total of 71 of the 72 patients completed the trial. The median treatment outcome score at 4 hours was 50.0 in the ecallantide group and 0.0 in the placebo group (interquartile range [IQR], 0.0 to 100.0 in both groups; P = 0.004). The median change in the mean symptom complex severity score at 4 hours was -1.00 (IQR, -1.50 to 0.00) with ecallantide, versus -0.50 (IQR, -1.00 to 0.00) with placebo (P = 0.01). The estimated time to significant improvement was 165 minutes with ecallantide versus more than 240 minutes with placebo (P = 0.14). There were no deaths, treatment-related serious adverse events, or withdrawals owing to adverse events. Conclusions: Four hours after administration of ecallantide or placebo for acute attacks of angioedema in patients with hereditary angioedema, patient-reported treatment outcome scores and mean symptom complex severity scores were significantly better with ecallantide than with placebo. (Funded by Dyax; ClinicalTrials.gov number, NCT00262080.)

Original languageEnglish (US)
Pages (from-to)523-531
Number of pages9
JournalNew England Journal of Medicine
Volume363
Issue number6
DOIs
StatePublished - Aug 5 2010
Externally publishedYes

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Hereditary Angioedemas
Placebos
Angioedema
Therapeutics
Plasma Kallikrein
Inborn Genetic Diseases
ecallantide
Double-Blind Method
Edema
Mucous Membrane
Skin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cicardi, M., Levy, R. J., McNeil, D. L., Li, H., Sheffer, A. L., Campion, M., ... Pullman, W. E. (2010). Ecallantide for the treatment of acute attacks in hereditary angioedema. New England Journal of Medicine, 363(6), 523-531. https://doi.org/10.1056/NEJMoa0905079

Ecallantide for the treatment of acute attacks in hereditary angioedema. / Cicardi, Marco; Levy, Robyn J.; McNeil, Donald L.; Li, Huamin; Sheffer, Albert L.; Campion, Marilyn; Horn, Patrick T.; Pullman, William E.

In: New England Journal of Medicine, Vol. 363, No. 6, 05.08.2010, p. 523-531.

Research output: Contribution to journalArticle

Cicardi, M, Levy, RJ, McNeil, DL, Li, H, Sheffer, AL, Campion, M, Horn, PT & Pullman, WE 2010, 'Ecallantide for the treatment of acute attacks in hereditary angioedema', New England Journal of Medicine, vol. 363, no. 6, pp. 523-531. https://doi.org/10.1056/NEJMoa0905079
Cicardi, Marco ; Levy, Robyn J. ; McNeil, Donald L. ; Li, Huamin ; Sheffer, Albert L. ; Campion, Marilyn ; Horn, Patrick T. ; Pullman, William E. / Ecallantide for the treatment of acute attacks in hereditary angioedema. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 6. pp. 523-531.
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AU - Campion, Marilyn

AU - Horn, Patrick T.

AU - Pullman, William E.

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N2 - Background: Hereditary angioedema is a rare genetic disorder characterized by acute, intermittent, and potentially life-threatening attacks of edema of the skin and mucosa. We evaluated ecallantide, a newly developed recombinant plasma kallikrein inhibitor, for the treatment of acute attacks of angioedema. Methods: In this double-blind, placebo-controlled trial, patients with hereditary angioedema presenting with an acute attack were randomly assigned, in a 1:1 ratio, to receive subcutaneous ecallantide, at a dose of 30 mg, or placebo. Two measures of patient-reported outcomes were used to assess the response: treatment outcome scores, which range from +100 (designated in the protocol as significant improvement in symptoms) to -100 (significant worsening of symptoms), and the change from baseline in the mean symptom complex severity score, which range from +2 (representing a change from mild symptoms at baseline to severe symptoms after) to -3 (representing a change from severe symptoms at baseline to no symptoms after). The primary end point was the treatment outcome score 4 hours after study-drug administration. Secondary end points included the change from baseline in the mean symptom complex severity score at 4 hours and the time to significant improvement. Results: A total of 71 of the 72 patients completed the trial. The median treatment outcome score at 4 hours was 50.0 in the ecallantide group and 0.0 in the placebo group (interquartile range [IQR], 0.0 to 100.0 in both groups; P = 0.004). The median change in the mean symptom complex severity score at 4 hours was -1.00 (IQR, -1.50 to 0.00) with ecallantide, versus -0.50 (IQR, -1.00 to 0.00) with placebo (P = 0.01). The estimated time to significant improvement was 165 minutes with ecallantide versus more than 240 minutes with placebo (P = 0.14). There were no deaths, treatment-related serious adverse events, or withdrawals owing to adverse events. Conclusions: Four hours after administration of ecallantide or placebo for acute attacks of angioedema in patients with hereditary angioedema, patient-reported treatment outcome scores and mean symptom complex severity scores were significantly better with ecallantide than with placebo. (Funded by Dyax; ClinicalTrials.gov number, NCT00262080.)

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