Dose‐Exposure‐Response Relationship of the Investigational Anti‐Interleukin‐13 Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma

Interleukin (IL)‐13 is involved in the pathogenesis of some types of asthma. Tralokinumab is a human immunoglobulin G 4 monoclonal antibody that specifically binds to IL‐13. Two placebo‐controlled phase II studies (phase IIa, NCT00873860 and phase IIb, NCT01402986) have been conducted in which tralokinumab was administered subcutaneously. This investigation aimed to characterize tralokinumab's dose‐exposure‐response (forced expiratory volume in 1 s (FEV 1 )) relationship in patients with asthma and to predict the most appropriate dose for phase III. An integrated population pharmacokinetic‐pharmacodynamic (PK/PD) modeling analysis was required for phase III dose selection, due to differing phase II patient populations, designs, and regimens. Analysis of combined datasets enabled the identification of tralokinumab's dose‐exposure‐FEV 1 response relationship in patients with asthma. Near‐maximal FEV 1 increase was predicted at a dose of 300 mg SC once every 2 weeks (Q2W). This dose was chosen for tralokinumab in the phase III clinical development program for treatment of severe, uncontrolled asthma.