A double-blind, placebo-controlled, multi-crossover trial of treatment with a chemokine antagonist for knee osteoarthritis pain

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.