Premium
A Phase 1, Randomized Ascending Single‐Dose Study of Antagonist Anti‐Human CD40 ASKP1240 in Healthy Subjects
Author(s) -
Goldwater R.,
Keirns J.,
Blahunka P.,
First R.,
Sawamoto T.,
Zhang W.,
Kowalski D.,
Kaibara A.,
Holman J.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12082
Subject(s) - medicine , pharmacokinetics , placebo , tolerability , pharmacodynamics , antagonist , pharmacology , gastroenterology , adverse effect , receptor , pathology , alternative medicine
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.