TY - JOUR
T1 - Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema
AU - Riedl, Marc A.
AU - Lumry, William R.
AU - Li, H. Henry
AU - Banerji, Aleena
AU - Bernstein, Jonathan A.
AU - Baş, Murat
AU - Björkander, Janne
AU - Magerl, Markus
AU - Maurer, Marcus
AU - Rockich, Kevin
AU - Chen, Hongzi
AU - Schranz, Jennifer
N1 - Publisher Copyright:
Copyright © 2016, OceanSide Publications, Inc., U.S.A.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
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U2 - 10.2500/aap.2016.37.4006
DO - 10.2500/aap.2016.37.4006
M3 - Article
C2 - 27931305
AN - SCOPUS:84995569472
SN - 1088-5412
VL - 37
SP - 489
EP - 500
JO - Allergy and Asthma Proceedings
JF - Allergy and Asthma Proceedings
IS - 6
ER -