Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema

Marc A. Riedl, William R. Lumry, H. Henry Li, Aleena Banerji, Jonathan A. Bernstein, Murat Baş, Janne Björkander, Markus Magerl, Marcus Maurer, Kevin Rockich, Hongzi Chen, Jennifer Schranz

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The currently approved method of C1 inhibitor (C1 INH) administration for patients with hereditary angioedema with C1 INH deficiency (HAE) is by intravenous injection. A C1 INH subcutaneous formulation may provide an attractive mode of administration for some patients. Objective: To evaluate efficacy and safety of two doses of subcutaneous, plasma-derived C1 INH with the dispersing agent, recombinant human hyaluronidase (rHuPH20) to prevent angioedema attacks in patients with HAE. Methods: A randomized, double-blind, dose-ranging, crossover study, patients ≥ 12 years of age (n = 47) with a confirmed diagnosis of HAE were randomly assigned to receive subcutaneous injections of 1000 U C1 INH with 24,000 U rHuPH20 or 2000 U C1 INH with 48,000 U rHuPH20 every 3 or 4 days for 8 weeks and then crossed-over for another 8-week period. The primary efficacy end point was the number of angioedema attacks during each treatment period. Results: The study was terminated early as a precaution related to non-neutralizing antibodies to rHuPH20 in 45% of patients. The mean ± standard deviation number of angioedema attacks during the 8-week treatment periods were 1.58 ± 1.59 with 1000 U C1 INH and 0.97 ± 1.26 with 2000 U. The mean (95% confidence interval [CI]) within-patient difference (2000 U-1000 U, respectively) was -0.61 (95% CI, -1.23 to 0.01) attacks per month (p = 0.0523), and -0.56 (95% CI, -1.06 to -0.05) attacks that required acute treatment, (p = 0.0315). No deaths or other serious adverse events were reported. Injection-site reaction was the most common adverse event. Conclusion: Despite early termination, this study demonstrated a clinically and statistically significant difference in burden of disease, which favored 2000 U C1 INH, without associated serious adverse events.

Original languageEnglish (US)
Pages (from-to)489-500
Number of pages12
JournalAllergy and Asthma Proceedings
Issue number6
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Immunology and Allergy


Dive into the research topics of 'Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema'. Together they form a unique fingerprint.

Cite this