Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study.
| Title: | Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study. |
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| Authors: | Li HH; 1Institute for Asthma and Allergy, 2 Wisconsin Cir #250, Chevy Chase, MD 20815 USA.; Zuraw B; 2UC San Diego School of Medicine, 9500 Gilman Dr., Mail code 0732, La Jolla, CA 92093-0732 USA.; Longhurst HJ; 3Addenbrooke's Hospital, Cambridge, CB2 0QQ UK.; Cicardi M; Ospedale Luigi Sacco/U.O. Medina Generale, Via G.B. Grassi, 74, 20157 Milan, Italy.; Bork K; 5Department of Dermatology, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.; Baker J; Baker Allergy, Asthma & Dermatology Research Center, LLC, 9495 SW Locust, Portland, OR 97223 USA.; Lumry W; AARA Research Center, 10100 N Central Expressway, Suite 125, Dallas, TX 75231 USA.; Bernstein J; 8Bernstein Clinical Research Center, LLC, 8444 Winton Road, Cincinnati, OH 45231 USA.; Manning M; Medical Research of Arizona, 7514 E Monterey Way, Suite-1A, Scottsdale, AZ 85251 USA.; Levy D; 705 West La Veta Avenue, Suite 101, Orange, CA 92868 USA.; Riedl MA; 11University of California-San Diego School of Medicine, 8899 University Center Lane, Suite 230, La Jolla, CA 92122 USA.; Feuersenger H; 12CSL Behring GmbH, Marburg, Germany.; Prusty S; 12CSL Behring GmbH, Marburg, Germany.; Pragst I; 12CSL Behring GmbH, Marburg, Germany.; Machnig T; 12CSL Behring GmbH, Marburg, Germany.; Craig T; 13Department of Medicine and Pediatrics, Penn State University Allergy, Immunology and Respiratory Research, 500 University Drive H041, Hershey, PA 17033 USA. |
| Corporate Authors: | COMPACT Investigators |
| Source: | Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology [Allergy Asthma Clin Immunol] 2019 Aug 28; Vol. 15, pp. 49. Date of Electronic Publication: 2019 Aug 28 (Print Publication: 2019). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Country of Publication: England NLM ID: 101244313 Publication Model: eCollection Cited Medium: Print ISSN: 1710-1484 (Print) Linking ISSN: 17101484 NLM ISO Abbreviation: Allergy Asthma Clin Immunol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: Oct. 2009- : London : BioMed Central; Original Publication: Hamilton, Ont. : BC Decker, c2004- |
| Abstract: | Background: Hereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment effects by subgroups, onset of effect, and other exploratory analysis have not been reported.; Methods: This is a post hoc exploratory analysis on data from the randomized, placebo-controlled COMPACT study. 90 patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH (SC) 40 or 60 IU/kg of body weight twice weekly for 16 weeks, preceded or followed by a placebo period. The pre-specified primary efficacy endpoint was the time-normalized number of HAE attacks, and pre-specified secondary efficacy endpoints were the percentage of patients with a certain treatment response (≥ 50% reduction on C1-INH (SC) versus placebo in the time-normalized number of attacks) and the time-normalized number of use of rescue medication. Pre-specified exploratory endpoints included severity of attacks, alone and combined with rescue medication use. Post hoc analyses included exploration of onset of effect and clinical assessment of patients with |
| Competing Interests: | Competing interestsHHL received institutional support from CSL Behring for the conduct of this study, and travel expenses and/or consultancy fees and speaker’s honoraria from CSL Behring, Shire/Dyax/ViroPharma, and Salix/Pharming. TC is a speaker for CSL Behring, Grifols and Dyax/Shire. He performs research for BioCryst, Boehringer Ingelheim, CSL Behring, Genentech, GlaxoSmithKline, Grifols, Merck, Novartis, Pharming, Sanofi, and Shire. He has received consultancy fees and/or speaker’s honoraria from BioCryst, Bellrose, CSL Behring, Dyax, Merck, Novartis, Pharming Technologies, and Shire, and has received non-financial support from CSL Behring, Shire, and Grifols. BZ reports grant support from the Department of Defense and consultancy fees from Alnylam, Arrowhead Pharmaceuticals, BioCryst Pharmaceuticals, Nektar, CSL Behring, and Shire, and led the Scientific Steering Committee for this study. HJL has received grant support from CSL Behring, consultancy fees, and speaker’s honoraria from CSL Behring, Pharming, and Shire, and travel support from CSL Behring. MC has received grants from Shire and personal fees from Alnylam, BioCryst Pharmaceuticals, CSL Behring, Dyax, KalVista Pharming Technologies, Shire, Sobi (Swedish Orphan Biovitrum), and ViroPharma. KB reports personal fees from CSL Behring and Shire, outside the submitted work. HB received consultancy fees and speaker’s honoraria from CSL Behring, Pharming, and Shire. WL reports grant support from BioCryst Pharmaceuticals, CSL Behring, and Shire/Viropharma/Dyax; consultancy fees paid to his institution from Adverum, BioCryst Pharmaceuticals, CSL Behring, Pharming Technologies, and Shire/Virophama/Dyax; speaker’s fees from Pharming Technologies, Shire/Viropharma and CSL Behring; and non-financial support from the US Hereditary Angioedema Association outside the submitted work. JB reports grant support and personal fees from BioCryst Pharmaceuticals, CSL Behring, and Shire, outside the submitted work. MM reports grant support and consultant/speaker’s fees from CSL Behring, Shire, Dyax, and Shire; and personal fees from Salix and Pharming Technologies, outside the submitted work. DL has served on the speaker’s bureau, as a consultant, on a steering committee, and as a clinical investigator for CSL Behring. MR has received research grants from BioCryst Pharmaceuticals, CSL Behring, Dyax, Pharming Technologies, and Shire; consultant fees from Adverum Biotechnologies, Alnylam Pharmaceuticals, BioCryst Pharmaceuticals, CSL Behring, Global Blood Therapeutics, Ionis Pharmaceuticals, KalVista Pharmaceuticals, Pharming Technologies, and Shire; speaker’s honoraria from CSL Behring, Shire, and Pharming; and is an uncompensated advisory board member for the US Hereditary Angioedema Association. TM, SP HF and IP are employees of CSL Behring. |
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| Contributed Indexing: | Keywords: C1-INH (SC); C1-esterase inhibitor protein; COMPACT study; HAEGARDA®; Hereditary angioedema; Long-term prophylaxis; Replacement therapy; Subcutaneous |
| Molecular Sequence: | ClinicalTrials.gov NCT01912456 |
| Entry Date(s): | Date Created: 20190906 Latest Revision: 20220410 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6714075 |
| DOI: | 10.1186/s13223-019-0362-1 |
| PMID: | 31485239 |
| Database: | MEDLINE |
Journal Article