Trevi Therapeutics, a late-stage clinical development company developing oral NalbuphineER for chronic pruritus conditions, has announced positive results from its phase II trial for the treatment of moderate to severe prurigo nodularis. Prurigo nodularis (PN), a severely pruritic dermatological condition characterized by itchy skin papules and nodules, has significant impact on quality of life and has no approved therapies. Trevi also previously reported statistically significant results from a robust phase II/III trial with Nalbuphine ER in hemodialysis patients with uremic pruritus.
The multicenter, randomized, double-blind, placebo-controlled, parallel, three-arm study evaluated the safety and anti-pruritic efficacy of Nalbuphine ER tablets dosed twice-daily at 90mg and 180mg in 62 patients in the U.S. and Europe. Patients with moderate-to-severe itch intensity, defined as ≥ 5 on the 0-10 Numerical Rating Score (NRS) scale, were enrolled to evaluate drug efficacy across a representative patient population for treatment of this chronic indication. The actual average baseline worst itch for enrolled patients was ≥ 8, indicating the severe nature of the disease.
The study consisted of a titration period of two weeks, followed by an eight-week blinded period on a fixed dose of drug or placebo, and a two-week wash-out period. At the end of the wash-out period, patients were eligible to roll over into a one-year open label extension study. The Company expects the open label extension study to be completed in the third quarter of 2017.
The main outcome variables for this study were responder analyses of the proportion of patients with at least a 30% or 50% reduction in their seven-day worst-itch intensity NRS from baseline to completion of treatment at week 10 or last observation visit. The proportion of patients in the Nalbuphine ER 180 mg BID arm meeting 50% responder criteria at week 10 or last observed visit (MITT population with n=18) approached statistical significance (p=0.083), and this arm met statistical significance for patients (n=12) completing treatment (p=0.028). The mean change in worst itch NRS was additionally evaluated, and the MITT population of the Nalbuphine ER 180 mg BID arm as compared to placebo approached statistical significance (p=0.083) as well. This arm also met statistical significance for patients (n=12) completing treatment (p=0.025).
The ItchyQoL secondary endpoint, 22 questions that measure how pruritus affects a patient’s quality of life, provided supportive evidence of a favorable treatment effect on reduction in itch intensity compared to placebo. Change from baseline in the ItchyQoL total score was significantly more favorable for the Nalbuphine ER 180 mg BID dose compared to placebo (p=0.022).
The most common adverse events in the study were dizziness, nausea, headaches, and fatigue, the majority of which were grade 1 or 2. As seen previously, the incidence rate of these events was similar to placebo after the titration period. No serious adverse events attributed to the drug were observed, and the study DSMB raised no issues that affected the continuation of the study or required modification of study procedures.
Jennifer L. Good, Trevi’s president and chief executive officer, said, “We have now demonstrated that Nalbuphine ER can improve pruritus in two very different and severe itch conditions: prurigo nodularis and uremic pruritus. Itch is a significant unmet medical need resulting from many diseases in dermatology, oncology, hepatology and neurology, and we believe Nalbuphine ER may provide an important therapy for these patients.”
Thomas R. Sciascia, M.D., Trevi’s chief medical officer, said, “Prurigo nodularis is a very serious dermatologic condition, with no approved therapies. Once a patient gets PN, they may cope with the disease for many years, with significant impact on their ongoing quality of life. We are pleased with the results of our trial, and are preparing for a discussion with both FDA and EMA about the development path forward with the critical mass of data we have gathered.”
Trevi is preparing for an end of phase II meeting for prurigo nodularis, has already held an end of phase II meeting with FDA for uremic pruritus, and will initiate phase III trials in both conditions in 2017. Founded in 2011, Trevi is headquartered in New Haven, CT.