Berotralstat for long-term prophylaxis of hereditary angioedema in Japan: Parts 2 and 3 of the randomized APeX-J Phase III trial.
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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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão