Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

Background: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1. Objective: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs and cellular infiltration in skin biopsies following epicutaneous nickel challenge in allergic subjects. Subjects/Methods: In this phase 1/2 study, 40 subjects were randomized to 5 days of treatment in four parallel groups (placebo three times daily (TID), placebo once daily (QD), 1000 mg CP-418 715 TID, and 3000 mg CP-418 715 QD). Twenty-four hours after the first drug administration, nickel sulfate patches were applied on subjects' backs and removed 48 hours later. Results: Pretreatment with 1000 mg CP-481715 TID resulted in significant reductions in visual scores of the nickel reactions (P = 0.01). Instrumentally measured erythema tended to decrease in the CP-481715 mg TID group (P = 0.06). No differences were noted between the 3000 mg CP-481715 mg QD group and pooled placebo. No significant differences were found for immunohistological cell counts. CP-418 715 was generally safe and well tolerated. Conclusions: Blocking of CCR1 only partly inhibited clinical manifestations of ACD. Several chemokine receptors are likely relevant for the cellular influx observed in ACD lesions.