Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2025
Safety and pharmacokinetics of long-acting plasma kallikrein inhibitor navenibart (STAR-0215) in healthy adults.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Lumry William, Gunsior Michele, Cohen Theodora, Bernard Kristine, Gustafson Pamela, Chung Jou-Ku, Morabito Christopher
Аннотация
BACKGROUND: Hereditary angioedema (HAE) is a rare, autosomal-dominant disorder characterized by bradykinin-mediated episodic, localized swelling that can be fatal. Currently approved long-term prophylactic therapies for HAE attacks incur substantial treatment burden through frequent dosing. Navenibart (STAR-0215) is a monoclonal antibody inhibitor of plasma kallikrein modified to extend circulating half-life and is under investigation for HAE prophylaxis.
OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of navenibart in healthy adults and to assess the feasibility of every 3- and 6-month dosing.
METHODS: In this phase 1a study, participants were randomized 3:1 to receive placebo or navenibart in escalating (100-1200 mg) dosing cohorts. Safety outcomes, including treatment-emergent adverse events (TEAEs) and serious AEs, were monitored until the end of the study (day 224). Additional end points included pharmacokinetic parameters and inhibition of plasma kallikrein activity.
RESULTS: In total, 31 participants received navenibart and 10 received placebo. The median age of the participants was 36 years; 53.7% were male; 51.2% were Black or African American. Rates of TEAEs were similar between navenibart and placebo, and no serious AEs were reported. Navenibart-related TEAEs included injection site reactions, inclusive of erythema, pruritus, and swelling, which resolved without intervention. For all doses more than or equal to 300 mg, navenibart mean half-life ranged from 82 to 105 days and inhibition of factor XIIa-induced plasma kallikrein activity vs placebo was statistically significant (P < .05). Statistically significant inhibition of factor XIIa-induced plasma kallikrein activity vs placebo (P < .05) was observed with all doses of navenibart.
CONCLUSION: In this first-in-human study, up to 1200 mg of navenibart was well tolerated and demonstrated an extended half-life with durable plasma kallikrein inhibition.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05477160.
OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of navenibart in healthy adults and to assess the feasibility of every 3- and 6-month dosing.
METHODS: In this phase 1a study, participants were randomized 3:1 to receive placebo or navenibart in escalating (100-1200 mg) dosing cohorts. Safety outcomes, including treatment-emergent adverse events (TEAEs) and serious AEs, were monitored until the end of the study (day 224). Additional end points included pharmacokinetic parameters and inhibition of plasma kallikrein activity.
RESULTS: In total, 31 participants received navenibart and 10 received placebo. The median age of the participants was 36 years; 53.7% were male; 51.2% were Black or African American. Rates of TEAEs were similar between navenibart and placebo, and no serious AEs were reported. Navenibart-related TEAEs included injection site reactions, inclusive of erythema, pruritus, and swelling, which resolved without intervention. For all doses more than or equal to 300 mg, navenibart mean half-life ranged from 82 to 105 days and inhibition of factor XIIa-induced plasma kallikrein activity vs placebo was statistically significant (P < .05). Statistically significant inhibition of factor XIIa-induced plasma kallikrein activity vs placebo (P < .05) was observed with all doses of navenibart.
CONCLUSION: In this first-in-human study, up to 1200 mg of navenibart was well tolerated and demonstrated an extended half-life with durable plasma kallikrein inhibition.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05477160.