Food allergy, anaphylaxis, dermatology, and drug allergyCritical role of kallikrein in hereditary angioedema pathogenesis: A clinical trial of ecallantide, a novel kallikrein inhibitor
Section snippets
Study design
The EDEMA1 study was a multicenter, randomized, placebo-controlled, double-blind, ascending-dose trial evaluating 4 doses of ecallantide in patients experiencing acute attacks of HAE. Patients were randomized to treatment with a single dose of ecallantide (5, 10, 20, or 40 mg/m2 intravenously) or placebo (PBS) by intravenous infusion. Twelve patients were assigned to each dose cohort, with 10 patients randomized to receive ecallantide and 2 to placebo. On the basis of the patient's calculated
Treatment assignments, patient demographics, and baseline characteristics
Forty-eight patients were randomized to intravenous treatment with ecallantide (n = 40, 83.3%) or to receive placebo (n = 8, 16.7%). Ten patients each were randomized to be treated with a dose of 5, 10, 20, or 40 mg/m2 ecallantide. As a result of the simultaneous HAE attacks of 2 patients at different study sites, an additional patient (40 mg/m2 ecallantide cohort) was enrolled beyond the protocol-designated population of 48 patients. Only 1 of these patients was randomized to treatment. The
Discussion
In this first placebo-controlled clinical trial of a kallikrein inhibitor to treat HAE, ecallantide was a safe and effective treatment. The primary efficacy endpoint of the study was achieved, with 72.5% of patients treated with ecallantide reporting significant improvement in symptoms within 4 hours compared with 25.0% of placebo patients (P = .0169). During the study, 5 patients treated with ecallantide and 3 patients who received placebo received additional medication for HAE symptoms on the
References (44)
Molecular genetics of C1 inhibitor
Immunobiology
(1998)- et al.
Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain
Ann Allergy Asthma Immunol
(2005) - et al.
Hereditary angioedema: a decade of management with stanozolol
J Allergy Clin Immunol
(1987) - et al.
Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience
J Allergy Clin Immunol
(1991) - et al.
Danazol-induced hepatocellular adenoma
Am J Med
(1990) - et al.
Adverse effects of danazol prophylaxis on the lipid profiles of patients with hereditary angioedema
J Allergy Clin Immunol
(2005) - et al.
Canadian 2003 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema
J Allergy Clin Immunol
(2004) - et al.
Does heparin prophylaxis prevent exacerbations of hereditary angioedema?
J Allergy Clin Immunol
(2002) - et al.
Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review
Transfus Apher Sci
(2003) Molecular genetics of C-inhibitor
Immunobiology
(1998)
The pathophysiology of hereditary angioedema
Clin Immunol
Bradykinin and the pathophysiology of angioedema
Int Immunopharmacol
Does C-2 kinin exist?
J Allergy Clin Immunol
Local bradykinin generation in hereditary angioedema
J Allergy Clin Immunol
Plasma bradykinin in angio-oedema
Lancet
Anaphylactic reaction and antibodies to DX-88 (kallikrein inhibitor) in a patient with hereditary angioedema
J Allergy Clin Immunol
Hereditary angioedema
N Engl J Med
Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients
Medicine
The C1 inhibitor deficiency
Eur J Clin Chem Clin Biochem
C1 Inhibitor deficiency: consensus document
Clin Exp Immunol
Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency
Arch Intern Med
Hereditary angioedema with gastrointestinal involvement: endoscopic appearance
Endoscopy
Cited by (0)
Supported by Dyax-Genzyme LLC.
Disclosure of potential conflict of interest: L. Schneider has consulting arrangements with and has received grant support from Dyax-Genzyme LLC. A. H. Williams used to be employed by Dyax Corp. W. Lumry has consulting arrangements with Abbott Laboratories, Alcon Laboratories, AstraZeneca, Boehringer Ingelheim, Dyax, Genentech, GlaxoSmithKline, Jerini, MedPointe, Merck, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Verus Pharmaceuticals; has received grant support from Abbott Laboratories, ICON Laboratories, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Dyaz, Dynavax, Genentech, GlaxoSmithKline, Immunex, IVAX, Jerini, Johnson & Johnson/Janssen, Lev Pharmaceuticals, MedPointe, Merck, Novartis, Pharmacia-Upjohn, Pfizer, Sanofi-Aventis, Schering-Plough, and Sepracor Pharmaceuticals; and is on the speakers' bureau for Abbott Laboratories, Alcon Laboratories, AstraZeneca, Boehringer Ingelheim, Dey Laboratories, Genentech, GlaxoSmithKline, KOS Pharmaceuticals, MedPointe, Merck, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Verus Pharmaceuticals. A. Vegh has received grant support from Dyax and is on the speakers' bureau for Schering-Plough, Merck, and IVAX. T. Schmalbach is employed by Dyax.