Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate

B. L. Zuraw, M. Cicardi, H. J. Longhurst, J. A. Bernstein, H. H. Li, M. Magerl, I. Martinez-Saguer, S. M.M. Rehman, P. Staubach, H. Feuersenger, R. Parasrampuria, J. Sidhu, J. Edelman, T. Craig

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57 Scopus citations


Background Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived C1-inhibitor (pdC1-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1-INH has not been studied in patients with HAE. Methods This open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1-INH functional activity, C1-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough C1-INH functional activity. Results After SC CSL830 administration, a dose-dependent increase in trough functional C1-INH activity was observed. C1-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event. Conclusions Subcutaneous volume-reduced CSL830 was well tolerated and led to a dose-dependent increase in physiologically relevant functional C1-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number10
StatePublished - Oct 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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