Erratum to: Human Plasma-Derived, Nanofiltered C1-Inhibitor Concentrate (Cinryze®), a Novel Therapeutic Alternative for the Management of Hereditary Angioedema Resulting From C1-Inhibitor Deficiency (original) (raw)
Related papers
Biologics in therapy, 2012
Hereditary angioedema resulting from the deficiency of the C1 inhibitor (HAE-C1-INH) is a rare, but potentially life-threatening disorder characterized by paroxysmal episodes of subcutaneous or submucosal edema. Early diagnosis is essential. Management is aimed at the prompt elimination of full-fledged attacks, as well as at the prevention of edematous episodes. The most straightforward means for therapy is supplementation with the deficient C1-INH protein. Placebo-controlled and open clinical studies have established that nanofiltered, human C1-INH concentrate, Cinryze® (ViroPharma Inc., Exton, PA, USA) (C1-INHCi), administered in 1,000 U doses is an effective and safe remedy for edematous episodes of HAE-C1-INH, regardless of the localization of the attack. Clinical manifestations rapidly improve and then resolve completely following treatment with this medicinal product. Additionally, C1-INHCi is also appropriate for pre-procedural or for routine prophylaxis. The administration o...
The journal of allergy and clinical immunology. In practice
Nanofiltered C1 inhibitor (human) is approved in the United States for routine prophylaxis of angioedema attacks in patients with hereditary angioedema, a rare disease caused by a deficiency of functional C1 inhibitor. To assess the safety of escalating doses of nanofiltered C1 inhibitor (human) in patients who were not adequately controlled on the indicated dose (1000 U every 3 or 4 days). Eligible patients had >1 attack/month over the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days for 12 weeks, at which point, the patients were evaluated. If treatment was successful (≤1 attack/mo) or at the investigator's discretion, the patients entered a 3-month follow-up period. The patients with an average of >1 attack/month were eligible for further escalation to 2000 U and then 2500 U. Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12 were escalated to 2500 U. Eighteen patients reported adverse events. Two patients reported 4 seriou...
Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor
The New England journal of medicine, 2017
Background Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. Methods We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly follow...
Clinical Immunology, 2012
From 1997, plasma-derived C1-inhibitor concentrate (Cetor®) has been available to HAE and AAE patients. Recently, a virus reducing 15 nm nanofiltration step has been introduced in the production process. A randomized, double-blind controlled cross-over study was performed to compare the pharmacokinetics (PK) of nanofiltered (C1-INH-NF) with conventional C1-inhibitor (C1-INH). Efficacy and safety were investigated in an open-label, on-demand and a prophylactic study. No differences in pharmacokinetic parameters between C1-INH and C1-INH-NF were found (13 non-symptomatic HAE patients). Both C1-inhibitor products equally increased plasma C4 levels. In the on-demand study, 14 acute angioedema attacks in 8 patients were analyzed. In the prophylactic study, 1 AAE and 5 HAE patients experienced in total 31 attacks during 748 observation days. In total 180,000 units of C1-INH-NF were administered. No product-related adverse events occurred, and no anti-C1-antibodies were induced. Nanofiltration in the production process of C1-inhibitor did not affect the pharmacokinetics, efficacy, and safety.
Journal of Allergy and Clinical Immunology, 2006
Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by C1-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause considerable delay in treatment and inconvenience for patients. Objective: The aim of this study was to investigate the feasibility, efficacy, and safety of on-demand and prophylactic self-administration of C1-inhibitor concentrate in patients with frequent attacks of angioedema. Methods: Patients with hereditary or acquired C1-inhibitor deficiency who had very frequent angioedema attacks were trained to self-administer C1-inhibitor concentrate. The study consisted of 31 patients using on-demand treatment and 12 patients using prophylaxis with C1-inhibitor concentrate. Mean follow-up was 3.5 years. Results: All patients were capable of self-administering the concentrate, with technical failure rates of self-injection being less than 2%. Times between the onset of the attack and the initiation of relief or complete resolution of symptoms in the on-demand group were significantly shortened (2.2 hours and 7.9 hours, respectively) compared with the situation before the start of self-administration. In the prophylaxis group self-administration of C1-inhibitor concentrate decreased the angioedema attack rate from 4.0 to 0.3 attacks per month. Conclusion: Intravenous self-administration of C1-inhibitor concentrate is a feasible and safe option and results in more rapid and more effective treatment or prevention of severe angioedema attacks in patients with C1-inhibitor deficiency. Clinical implications: Self-administration of C1-inhibitor concentrate could be a valuable and convenient treatment modality to prevent or treat angioedema attacks in patients with C1-inhibitor deficiency. (J Allergy Clin Immunol 2006;117:904-8.)
Safety and Usage of C1-Inhibitor in Hereditary Angioedema: Berinert Registry Data
The journal of allergy and clinical immunology. In practice, 2016
The plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; "pnfC1-INH") is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis. The objective of this study was to describe safety and usage patterns of pnfC1-INH. A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety and usage data on subjects receiving pnfC1-INH for any reason. Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No...
The Journal of Allergy and Clinical Immunology: In Practice, 2019
fees/ honorarium from CSL Behring and Shire/ViroPharma and Pharming; consulting fees/honorarium from BioCryst and Adverum; support for travel to meetings for the study or other purposes from CSL Behring and the United States Hereditary Angioedema Association; and fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like from BioCryst. M. Cicardi has received research grants, is an advisory board member, and has served as a speaker for Shire and Pharming; he has served as an advisory board member and speaker for CSL Behring and BioCryst. B. Zuraw has served as a consultant for CSL Behring, Shire, BioCryst, Adverum, Novartis, Sanofi, and Genentech; he has worked in a research support capacity for Ionis. J. A. Bernstein reports grants and personal fees from Shire; grants and personal fees from CSL Behring; grants and personal fees from Pharming; grants and personal fees from BioCryst, from HAEA medical advisory board, during the conduct of the study; grants and personal fees from Novartis/Genentech; and grants and personal fees from AstraZeneca, outside the submitted work. J. Anderson reports personal fees and other from Shire; other from Dyax; personal fees and other from CSL Behring; personal fees from Pharming; and other from BioCryst, outside the submitted work. J. Jacobs has received research grants, consulting fees, and honoraria from Shire plc, CSL Behring, Pharming, and BioCryst. M. A. Riedl has served in a research support capacity for BioCryst, CSL Behring, Pharming, and Shire; he has received consulting fees from BioCryst, CSL Behring, Shire, Pharming, Kalvista, and Adverum; and honorarium for speaking from CSL Behring, Pharming, and Shire. M. E. Manning reports grants and personal fees from Shire; grants from Dyax; grants and personal fees from CSL Behring; personal fees from Pharming; and grants from BioCryst, outside the submitted work. A. Banerji has received research grants from Shire and BioCryst; she served on advisory boards for Shire, BioCryst, CSL Behring, and Pharming. R. G. Gower reports grants and personal fees from CSL Behring; grants and personal fees from Shire/Dyax; grants from BioCryst; and grants and personal fees from Pharming/ Salix, outside the submitted work. T. Caballero has received speaker fees from CSL Behring, Novartis, and Shire; consultancy fees from BioCryst, CSL Behring, Novartis, Octapharma, and Shire; funding for travel and meeting attendance from CSL Behring, Novartis, and Shire; and has participated in clinical trials/registries for BioCryst, CSL Behring, Novartis, and Shire. She is a researcher for the IdiPaz program promoting research activities. H. Farkas has received research support from Shire; is on the advisory boards for CSL Behring, Shire, BioCryst, and Swedish Orphan Biovitrum (SOBI); and has received consultancy fee from CSL Behring, Shire, BioCryst, and SOBI and speaker fee from CSL Behring, Pharming Group, and SOBI. H. Feuersenger reports personal fees from employment by CSL Behring (funding company), outside the submitted work. I. Jacobs reports personal fees from employment by CSL Behring (funding company), outside the submitted work. T. Machnig reports personal fees from employment by CSL Behring (funding company), outside the submitted work. H. Longhurst has
Clinical & Experimental Allergy
Background: Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. Objective: To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA ® ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics. Methods: C1-INH functional activity data obtained after administration of various C1-INH (intravenous; IV) and C1-INH (SC) doses from 1 study in healthy volunteers (n = 16) and 2 studies in subjects with HAE (n = 108) were pooled to develop a
Nanofiltered C1 Inhibitor Concentrate for Treatment of Hereditary Angioedema
New England Journal of Medicine, 2010
PURPOSE OF THE STUDY. To examine the efficacy of transfusion of autologous genetically modified hematopoietic stem cells for Wiskott-Aldrich syndrome (WAS). WAS is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity.