Population PK-PD analyses of CD25 occupancy, CD56^bright NK cell expansion, and regulatory T cell reduction by daclizumab HYP in subjects with multiple sclerosis.

ABSTRACT:

Aim

Daclizumab high yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α-subunit of the interleukin-2 receptor and is being developed for treatment of multiple sclerosis (MS). This manuscript characterized the pharmacokinetic-pharmacodynamic (PK-PD) relationships of daclizumab HYP in subjects with MS.

Methods

Approximately 1400 subjects and 7000 PD measurements for each of three biomarkers [CD25 occupancy, CD56^bright natural killer (NK) cell count, regulatory T cell (Treg) count] from four clinical trials were analyzed using non-linear mixed effects modelling. Evaluated regimens included 150 or 300 mg subcutaneous (s.c.) every 4 weeks.

Results

CD25 occupancy was characterized using a sigmoidal maximum response (E_max ) m

SUBMITTER: Diao L 

PROVIDER: S-EPMC5061794 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature