A Phase 1 Dose‐Escalation Study of ASP2409, a Selective T‐Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy

Abstract

ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.001 to 3.0 mg/kg to receive either ASP2409 or placebo in a sequential manner. Escalation to higher dose levels occurred in the absence of dose-limiting toxicity. A total of 57 patients completed the study. ASP2409 showed nonlinear PK over the dose range of 0.01 to 3.0 mg/kg following a single intravenous administration, indicating target-mediated drug disposition. Area under the concentration-time curve (AUC) and maximum concentration (Cmax ) increased at a greater than dose-proportional rate. The half-life of ASP2409 increased dose dependently and ranged from 1.57 to 6.68 days. ASP2409 showed a dose-dependent increase in the extent and duration of CD86 receptor occupancy. There were no clinically relevant safety issues up to a single dose of 3.0 mg/kg. No maximum tolerated dose was reached. The incidence and duration of antidrug antibodies did not correlate with adverse events. ClinicalTrials.gov identifier: NCT02171143.

Recent Advances in Nanotheranostics for Treat‐to‐Target of Rheumatoid Arthritis

“…In addition, remarkable attention has been paid to explore potential efficacy of a new monoclonal antibody. Zhang et al assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in the first‐in‐human study with higher binding avidity and selectivity to CD86 184. Furthermore, even in clinical trials, more types of nanomedicines will be found to reduce dose and frequency of dosing to achieve minimal adverse reactions and maximal treatment outcomes.…”

Role of biological agents in treatment of rheumatoid arthritis

“…ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. A phase I trial of ASP2409 in RA showed that this agent is tolerable and further clinical trials are pending [20].…”