A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody in subjects with plaque psoriasis

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Abstract
Objective: To evaluate safety, pharmacokinetics, pharmacodynamics, and clinical response of single subcutaneous (SC) administrations of a human mono­clonal antibody against the p40 subunit of IL‑12/23 (IL‑12/23 mAb) in subjects with moderate-to-severe psoriasis.Methods: Twenty-one subjects were enrolled sequentially into 4 dose cohorts (0.27, 0.675, 1.35, and 2.7 mg/kg) and randomized to IL‑12/23 mAb or placebo in a 4:1 ratio. Laboratory/clinical parameters and pharm­acokinetics were evaluated through Week 24; mRNA cytokine expression was measured in psoriatic plaques at Week 1.Results: Mostly mild adverse events and no serious adverse events were reported. The pharmacokinetics (Cmax and AUC) of IL‑12/23 mAb increased in an approximately dose-proportional manner. Of the 17 subjects who received IL‑12/23 mAb, 13 achieved PASI 75 (compared with no placebo subjects). mRNA expression of IL‑8, IL‑18, and IFN‑γ in psoriatic plaques decreased in subjects with sustained Psoriasis Area and Severity Index (...