Cara Therapeutics, Inc. (Nasdaq:CARA), a biotechnology company focused on developing and commercializing new chemical entities designed to selectively target peripheral kappa opioid receptors, has announced statistically significant topline results from its Phase II trial of its lead kappa opioid agonist, CR845, for the treatment of moderate to severe uremic pruritus (UP).
Uremic pruritus is a chronic systemic itch condition in patients with renal failure, often receiving hemodialysis. There are currently no approved products in the United States for the condition.
"These results demonstrate the potential of our lead candidate CR845 to address an additional indication of significant unmet need beyond our lead I.V. CR845 program in acute pain," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "With this encouraging data, we plan to engage the FDA in a formal meeting to guide the structure of a potential Phase III pivotal trial, which we would expect to begin in 2016."
The Phase II trial was a double‐blind, randomized, placebo‐controlled trial designed to evaluate the efficacy of I.V. CR845 compared to placebo in reducing the intensity of itch in dialysis patients over a two-week dosing period. The trial enrolled 65 dialysis patients at multiple sites in the United States.
The primary endpoint of the Phase II trial was the change from baseline of the average worst itching during the second week of treatment, as recorded on a visual analog scale (VAS). Patients receiving I.V. CR845 experienced a 54 per cent greater reduction in worst itch scores than those receiving placebo (p-value = 0.016), with an average reduction of -48 per cent from baseline as measured by the VAS. I.V. CR845-treated patients exhibited statistically significant reductions in both daytime (-51 per cent, p=0.03) and night time (-75 per cent, p=0.007) worst itch scores compared to placebo treatment.
Secondary endpoints focused on quality of life measures associated with pruritus using a series of previously validated self assessment scales, including the Skindex 10 score. Patients receiving I.V. CR845 experienced a 71 per cent greater reduction in the average total Skindex 10 score at the end the two-week treatment period than those receiving placebo (p-value=0.031).
The total score average included positive trends in patients receiving I.V. CR845 for each of the three Skindex 10 domains: disease, mood/emotional distress (statistically significant reduction, p-value = 0.046) and social functioning. Another secondary measure, itch-related sleep disturbances based on the Itch MOS Sleep Problems Index II, showed a positive trend in patients receiving I.V. CR845, with a 62 per cent improvement compared to placebo, although this trend was not observed to be statistically significant.
I.V. CR845 was shown to be safe and well tolerated during the study with no CR845-related serious adverse events (AEs reported. The most common AEs were transient numbness and dizziness, with no episodes of the CNS side effects (e.g.,
dysphoria and hallucinations) that have impeded the development of centrally-acting kappa opioids.
"The results of the CR845 Phase II study are very encouraging. The data demonstrate a robust effect of reducing both daytime and nocturnal itching by an objective scoring system as well as anecdotal quality of life histories," said Dr. James Tumlin, Professor, Department of Medicine, University of Tennessee and a Principal Investigator on the trial. "With no approved therapy and the limited efficacy of current options, CR845 provides an opportunity to alleviate the pain and discomfort of this persistent clinical problem among ESRD patients."
There are more than 400,000 patients in the United States and 2.2 million globally undergoing hemodialysis and it is estimated that as many as 50 per cent of these patients suffer from renal or uremic pruritus. Currently, there are no approved products in the United States for the condition, which can often be severe and resistant to treatment with traditional itch treatments, such as corticosteroids and antihistamines.
"We are excited by these topline results in uremic pruritus, which show that I.V. CR845 holds significant clinical potential in this indication of significant unmet need for dialysis patients," said Joseph Stauffer, D.O., M.B.A., Chief Medical Officer of Cara Therapeutics. "I.V. CR845 demonstrated a statistically significant effect, not only on our primary endpoint of reducing the itch intensity for dialysis patients, but also in important quality of life measurements, along with a favorable safety and tolerability profile."