title: Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, US HAEA Angioedema Center, University of CaliforniaSan Diego School of Medicine, La Jolla, California, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Riedl
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.forename: Aleena
authors.initials: A
authors.lastname: Banerji
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: Murat
authors.initials: M
authors.lastname: Ba
authors.forename: Janne
authors.initials: J
authors.lastname: Bjrkander
authors.forename: Markus
authors.initials: M
authors.lastname: Magerl
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Kevin
authors.initials: K
authors.lastname: Rockich
authors.forename: Hongzi
authors.initials: H
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schranz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein; D007518:Isoantibodies; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase