Trevi Therapeutics, a late-stage clinical development company developing oral Nalbuphine ER for chronic pruritus conditions, has reported positive results from its Phase 2 trial for the treatment of moderate-to-severe prurigo nodularis (PN).
PN is a severely pruritic dermatological condition characterised by itchy skin papules and nodules. It has a significant impact on quality of life and has no approved therapies.
Trevi previously reported significant results from a Phase 2/3 trial with Nalbuphine ER in hemodialysis patients with uremic pruritus.
The multi-centre, randomised, double-blind, placebo-controlled, parallel, three-arm study analysed the safety and anti-pruritic efficacy of Nalbuphine ER tablets dosed twice-daily at 90mg and 180mg in 62 patients within the US and Europe.
Patients with moderate-to-severe itch intensity defined as greater than 5 on the 0-10 Numerical Rating Score (NRS) scale were enrolled to evaluate drug efficacy.
The actual average baseline worst itch for enrolled patients was greater than 8, thereby showing the severe nature of the disease.
The trial covered a titration period of two weeks. It was 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.
Trevi 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 ten or last observation visit.
The proportion of patients in the Nalbuphine ER 180mg BID arm meeting 50% responder criteria at week ten 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 180mg BID arm compared to placebo also approached statistical significance (p=0.083).
This arm additionally met statistical significance for patients (n=12) completing treatment (p=0.025).
The most common adverse events in the study were dizziness, nausea, headaches, and fatigue.
Trevi president and chief executive officer Jennifer L Good 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.”
Trevi chief medical officer Thomas R. Sciascia 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 2 meeting for prurigo nodularis and has already held an end of Phase 2 meeting with FDA for uremic pruritus.
It will initiate Phase 3 trials in both conditions in 2017.