Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks.
J Alzheimers Dis
; 76(3): 967-979, 2020.
Article
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| MEDLINE
| ID: mdl-32568196
ABSTRACT
BACKGROUND:
Crenezumab is a fully humanized, monoclonal anti-amyloid-ß immunoglobulin G4 antibody.OBJECTIVE:
This Phase Ib study (NCT02353598) evaluated the safety, tolerability, and pharmacokinetics of crenezumabat doses of ≤120âmg/kg administered intravenously every 4 weeks (q4w). Immunogenicity and exploratory biomarkers were also evaluated.METHODS:
In this multicenter, double-blind study, participants (aged 50-90 years) with mild-to-moderate Alzheimer's disease (AD) and amyloid-positive positron emission tomography (PET) scan were randomized to receive crenezumab 30 or 45âmg/kg (Cohort 1, nâ=â21), 60âmg/kg (Cohort 2, nâ=â21), or 120âmg/kg (Cohort 3, nâ=â19) or corresponding placebo (nâ=â14) intravenously q4w for 13 weeks. Seventy-one participants were subsequently enrolled in an optional open-label extension (OLE) and received crenezumab at the originally assigned dose level, except for Cohort 3 (crenezumab 60âmg/kg during OLE). Participants received regular brain MRIs to assess amyloid-related imaging abnormalities (ARIA). Results up to Week 133 are reported.RESULTS:
Approximately 94% of participants experienced ≥1 adverse event (AE). Most AEs were mild or moderate; 15.5% experienced a Grade ≥3 AE. No ARIA-edema/effusion (ARIA-E) events were observed. New ARIA-micro hemorrhages and hemosiderosis (ARIA-H) were reported in 4.9% (double-blind treatment period) and 9.9% (combined double-blind treatment and OLE periods) of participants. Steady-state trough concentrations of crenezumab were dose-proportional and maintained for each dose level.CONCLUSION:
Crenezumab doses of ≤120âmg/kg intravenously q4w were well tolerated. The observed safety profile for ≤133 weeks of treatment in a mild-to-moderate AD population was similar to that seen in previous trials.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Resultado del Tratamiento
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Enfermedad de Alzheimer
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Anticuerpos Monoclonales Humanizados
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2020
Tipo del documento:
Article