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

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 (C_max 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 (PASI) improvement.

Limitations: Interpretation of results is limited due to the small sample size in each dose cohort.

Conclusion: A single SC administration of IL‑12/23 mAb was well tolerated and showed clinical response in subjects with moderate-to-severe psoriasis.

Key words: :

• CNTO1275
• IL-12/23 mAb
• Interleukin-12
• Interleukin-23
• Psoriasis