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Berotralstat for long-term prophylaxis of hereditary angioedema in Japan: Parts 2 and 3 of the randomized APeX-J Phase III trial.
Honda, Daisuke; Hide, Michihiro; Fukuda, Tomoo; Koga, Keisuke; Morita, Eishin; Moriwaki, Shinichi; Sasaki, Yoshihiro; Suzuki, Yusuke; Collis, Phil; Johnston, Douglas T; Tomita, Dianne; Desai, Bhavisha; Ohsawa, Isao.
Afiliação
  • Honda D; Department of Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan.
  • Hide M; Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
  • Fukuda T; Department of Dermatology, Hiroshima University, Hiroshima, Japan.
  • Koga K; Department of Dermatology, Saitama Medical Center, Kawagoe, Japan.
  • Morita E; Koga Community Hospital, Shizuoka, Japan.
  • Moriwaki S; Shimane University Hospital, Shimane, Japan.
  • Sasaki Y; Department of Dermatology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
  • Suzuki Y; National Hospital Organization Disaster Medical Center, Tokyo, Japan.
  • Collis P; Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan.
  • Johnston DT; Divison of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • Tomita D; BioCryst Pharmaceuticals, Inc., Durham, NC, United States.
  • Desai B; BioCryst Pharmaceuticals, Inc., Durham, NC, United States.
  • Ohsawa I; BioCryst Pharmaceuticals, Inc., Durham, NC, United States.
World Allergy Organ J ; 17(3): 100882, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38445295
ABSTRACT

Background:

Berotralstat is a once-daily oral inhibitor of plasma kallikrein for the prophylaxis of hereditary angioedema (HAE) in patients ≥12 years. APeX-J aimed to evaluate the efficacy and safety of berotralstat in Japan.

Methods:

APeX-J was a Phase III trial comprising 3 parts (NCT03873116). Part 1 was a randomized, placebo-controlled evaluation of berotralstat 150 or 110 mg over 24 weeks. Part 2 was a 28-week dose-blinded phase in which berotralstat-treated patients continued the same dose and placebo patients were re-randomized to berotralstat 150 or 110 mg. In Part 3, all patients remaining on study received berotralstat 150 mg in an open-label manner for up to an additional 52 weeks. The primary endpoint of Parts 2 and 3 was long-term safety and tolerability, and secondary endpoints examined effectiveness.

Results:

Seventeen patients entered Part 2, and 11 continued into Part 3. Treatment-emergent adverse events (TEAEs) were reported by 14/17 patients (82.4%) in Parts 2 or 3; the most common were nasopharyngitis, abdominal pain, cystitis, influenza, and vertigo. One patient (5.9%) experienced a drug-related TEAE (Grade 4 increased hepatic enzyme). No drug-related serious TEAEs were reported. For patients who completed 26 months of treatment with berotralstat 150 mg (n = 5), mean (standard error of the mean) monthly HAE attack rates and on-demand medication use decreased from baseline by 1.15 (0.09) attacks/month and 2.8 (0.64) doses/month, respectively. Sustained improvements were also observed in patient quality of life and treatment satisfaction.

Conclusions:

Long-term prophylaxis with berotralstat raised no new safety signals and was effective at reducing attacks and improving patient-reported outcomes. Trial registration ClinicalTrials.gov NCT03873116. Registered March 13, 2019. Retrospectively registered.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: World Allergy Organ J Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: World Allergy Organ J Ano de publicação: 2024 Tipo de documento: Article