Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

被引：112

作者：

Zuraw, Bruce ^{[1
]}

Lumry, William R. ^{[2
]}

Johnston, Douglas T. ^{[3
]}

Aygoren-Pursun, Emel ^{[4
]}

Banerji, Aleena ^{[5
]}

Bernstein, Jonathan A. ^{[6
]}

Christiansen, Sandra C. ^{[1
]}

Jacobs, Joshua S. ^{[7
]}

Sitz, Karl V. ^{[8
]}

Gower, Richard G. ^{[9
]}

Gagnon, Remi ^{[10
]}

Wedner, H. James ^{[11
]}

Kinaciyan, Tamar ^{[12
]}

Hakl, Roman ^{[13
,14
]}

Hanzlikova, Jana ^{[15
]}

Anderson, John T. ^{[16
]}

McNeil, Donald L. ^{[17
]}

Fritz, Stephen B. ^{[18
]}

Yang, William H. ^{[19
]}

Tachdjian, Raffi ^{[20
]}

Busse, Paula J. ^{[21
]}

Craig, Timothy J. ^{[22
]}

Li, H. Henry ^{[23
]}

Farkas, Henriette ^{[24
]}

Best, Jessica M. ^{[25
]}

Clemons, Desiree ^{[25
]}

Cornpropst, Melanie ^{[25
]}

Dobo, Sylvia M. ^{[25
]}

Iocca, Heather A. ^{[25
]}

Kargl, Deborah ^{[25
]}

Nagy, Eniko ^{[25
]}

Murray, Sharon C. ^{[25
]}

Collis, Phil ^{[25
]}

Sheridan, William P. ^{[25
]}

Maurer, Marcus ^{[26
]}

Riedl, Marc A. ^{[1
]}

机构：

[1] Univ Calif San Diego, San Diego, CA 92103 USA

[2] Allergy & Asthma Specialists Dallas, Dallas, TX USA

[3] Asthma & Allergy Specialists, Charlotte, NC USA

[4] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Frankfurt, Germany

[5] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

[6] Univ Cincinnati, Cincinnati, OH USA

[7] Allergy & Asthma Clin Res, Walnut Creek, CA USA

[8] Little Rock Allergy & Asthma Clin Res Ctr, Little Rock, AR USA

[9] Univ Washington Sch Med, Marycliff Clin Res, Spokane, WA USA

[10] Clin Specialisee Allergie Capitale, Quebec City, PQ, Canada

[11] Washington Univ Sch Med, St Louis, MO USA

[12] Med Univ Vienna, Dept Dermatol, Vienna, Austria

[13] Masaryk Univ, Dept Clin Immunol & Allergol, St Annes Univ Hosp Brno, Brno, Czech Republic

[14] Masaryk Univ, Fac Med, Brno, Czech Republic

[15] Fac Hosp, Dept Allergol & Immunol, Plzen, Czech Republic

[16] Clin Res Ctr Alabama, Birmingham, AL USA

[17] Optimed Res Ltd, Columbus, OH USA

[18] Portland Clin Res, Portland, OR USA

[19] Univ Ottawa, Ottawa Allergy Res Corp, Dept Med, Ottawa, ON, Canada

[20] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA

[21] Icahn Sch Med Mt Sinai, Dept Med, Div Clin Immunol & Allergy, New York, NY 10029 USA

[22] Penn State Univ, Dept Med & Pediat, Hershey, PA USA

[23] Inst Asthma & Allergy, Chevy Chase, MD USA

[24] Semmelweis Univ, Dept Internal Med 3, Hungarian Angioedema Reference Ctr, Budapest, Hungary

[25] BioCryst Pharmaceut, Durham, NC USA

[26] Charit Univ Med Berlin, Dept Dermatol & Allergy, Dermatol Allergol, Berlin, Germany

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2021年 / 148卷 / 01期

基金：

美国国家卫生研究院;

关键词：

BCX7353; berotralstat; C1; inhibitor; efficacy; HAE; hereditary angioedema; kallikrein inhibitor; long-term prophylaxis; prophylaxis; safety; QUALITY-OF-LIFE; PATHOPHYSIOLOGY; INHIBITOR; THERAPIES; BURDEN;

D O I：

10.1016/j.jaci.2020.10.015

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P<.001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

引用

页码：164 / +

页数：18

共 20 条

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