A phase 1, randomized ascending single-dose study of antagonist anti-human CD40 ASKP1240 in healthy subjects.
Am J Transplant
; 13(4): 1040-1046, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23356210
This first-in-human, phase I study evaluated the safety, tolerability, pharmacokinetic and pharmacodynamic profile of ASKP1240 in healthy subjects. Twelve sequential groups (each 6 active and 3 placebo) were randomly assigned to placebo or single ascending doses of intravenous ASKP1240 (0.00003-10 mg/kg). ASKP1240 exhibited nonlinear pharmacokinetics, with mean maximal serum concentrations and area under the serum concentration-time curves ranging from 0.7 to 251.6 µg/mL and 6.5 to 55409.6 h·µg/mL following doses 0.1 mg/kg-10 mg/kg, respectively. CD40 receptor occupancy by ASKP1240, which was dose-dependent, reached a maximum at doses above 0.01 mg/kg. ASKP1240 was well tolerated, with no evidence of cytokine release syndrome or thromboembolic events. Treatment emergent antibodies to ASKP1240 were detected in 5/70 (7.1%) ASKP1240 recipients. In conclusion, antagonism of the CD40/CD154 interaction with ASKP1240 was safe and well tolerated at the doses tested.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos CD40
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Inmunosupresores
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Anticuerpos Monoclonales
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Estados Unidos