A computational framework for complex disease stratification from multiple large-scale datasets.

Background: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states.

Safety and pharmacokinetics of olokizumab, an anti-IL-6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study.

Interleukin-6 (IL-6) is implicated in the pathophysiology of several inflammatory conditions. Olokizumab, a humanized anti-IL-6 monoclonal antibody, selectively blocks the final assembly of the IL-6 signaling complex. A randomized, double-blind, placebo-controlled, phase I dose-escalation study assessed the safety and tolerability of escalating single doses of olokizumab administered intravenously (iv) or subcutaneously (sc) to 67 healthy male volunteers.

Model-Based Optimal Design and Execution of the First-Inpatient Trial of the Anti-IL-6, Olokizumab.

The first-in-patient study for olokizumab (OKZ) employed model-based, optimal design and adaptive execution to define the concentration-C-reactive protein (CRP) suppression response. Modeling and exploratory statistics activities involved: reverse engineering of first-in-class (tocilizumab) pharmacokinetic/pharmacodynamic (PK/PD) models, adaptation of models to OKZ with a priori knowledge and preclinical data translation, application of multidimensional Desirability Index for optimal study design, sample size reestimation based on new information, optimization of second study part via Bayesian analysis of interim data, and interim and final analysis for PK/PD objective attainment. Design work defined a dose window (0.

Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study.

Objectives: The aim of this 12-week Phase IIb study was to assess the efficacy and safety of olokizumab (OKZ), a humanised anti-IL6 monoclonal antibody, in patients with rheumatoid arthritis (RA) with moderate-to-severe disease activity who had previously failed tumour necrosis factor (TNF) inhibitor therapy. The dose-exposure-response relationship for OKZ was also investigated.

Methods: Patients were randomised to one of nine treatment arms receiving placebo (PBO) or OKZ (60, 120 or 240 mg) every 4 weeks (Q4W) or every 2 weeks (Q2W), or 8 mg/kg tocilizumab (TCZ) Q4W.

Leveraging systems biology approaches in clinical pharmacology.

Computational modeling has been adopted in all aspects of drug research and development, from the early phases of target identification and drug discovery to the late-stage clinical trials. The different questions addressed during each stage of drug R&D has led to the emergence of different modeling methodologies. In the research phase, systems biology couples experimental data with elaborate computational modeling techniques to capture lifecycle and effector cellular functions (e.