TY  - JOUR
A1  - Riedl, Marc A.
A1  - Aygören-Pürsün, Emel
A1  - Baker, James
A1  - Farkas, Henriette
A1  - Anderson, John
A1  - Bernstein, Jonathan A.
A1  - Bouillet, Laurence
A1  - Busse, Paula J.
A1  - Manning, Michael
A1  - Magerl, Markus
A1  - Gompels, Mark
A1  - Huissoon, Aarn P.
A1  - Longhurst, Hilary
A1  - Lumry, William
A1  - Ritchie, Bruce
A1  - Shapiro, Ralph
A1  - Soteres, Daniel
A1  - Banerji, Aleena
A1  - Cancian, Mauro
A1  - Johnston, Douglas T.
A1  - Craig, Timothy
A1  - Launay, David
A1  - Li, Henry
A1  - Liebhaber, Myron
A1  - Nickel, Timothy
A1  - Offenberger, Jacob
A1  - Rae, William
A1  - Schrijvers, Rik
A1  - Triggiani, Massimo
A1  - Wedner, H. James
A1  - Dobo, Sylvia
A1  - Cornpropst, Melanie
A1  - Clemons, Desiree
A1  - Fang, Lei
A1  - Collis, Phil
A1  - Sheridan, William P.
A1  - Maurer, Marcus
T1  - Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial : the OPuS‐2 study
T2  - Allergy
N2  - Background: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐INH‐HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.
Methods: OPuS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks.
Results: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.
Conclusions: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐INH‐HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
KW  - C1 inhibitor
KW  - hereditary angioedema
KW  - oral kallikrein inhibitor
KW  - prophylaxis
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50860
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-508601
SN  - 1398-9995
SN  - 0105-4538
N1  - This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
VL  - 73
IS  - 9
SP  - 1871
EP  - 1880
PB  - Blackwell Munksgaard
CY  - Oxford
ER  -