Trevi Therapeutics announces positive results for Haduvio in Phase 2b CORAL study

Trevi Therapeutics, Inc., a clinical-stage biopharmaceutical company, has reported a positive outcome from the planned sample size re-estimation (SSRE) for its ongoing Phase 2b trial. Designed to evaluate the investigational therapy Haduvio (oral nalbuphine ER) for chronic cough treatment in patients with idiopathic pulmonary fibrosis (IPF), the trial’s current sample size of 160 patients remains unchanged following an interim statistical review.

The trial has already reached 75% of its enrollment target, with topline results anticipated in the first half of 2025. The SSRE analysis, which reviewed data from patients receiving the highest dose of Haduvio (108mg twice daily), confirmed the trial’s ability to achieve its primary efficacy endpoint without requiring an increase in participants.

Independent Review Supports Trial Design

The SSRE analysis, conducted after 50% of patients completed six weeks of treatment, reaffirmed the Phase 2b trial design and statistical power. Jennifer Good, President and CEO of Trevi Therapeutics, emphasized that this outcome supports the efficacy assumptions from prior studies, particularly the Phase 2a CANAL trial. Good noted that this milestone underscores Haduvio’s potential as a first-in-class chronic cough treatment for IPF patients, a condition with no approved therapies.

CORAL Trial Design and Objectives

The CORAL trial is a randomized, double-blind, placebo-controlled study comparing three doses of Haduvio (27mg, 54mg, and 108mg) against placebo over six weeks. It includes a two-week titration phase followed by a four-week fixed dosing period. The trial’s primary goal is to measure the relative change in 24-hour cough frequency using the VitaloJAK® cough monitor. Secondary outcomes include patient-reported measures of cough severity.

Chronic Cough in IPF: A Pressing Unmet Need

Chronic cough significantly impacts up to 85% of patients with idiopathic pulmonary fibrosis, a disease that affects approximately 140,000 individuals in the United States. Patients with this condition may cough as many as 1,500 times per day, worsening their overall prognosis and quality of life. This highlights the urgent need for a dedicated chronic cough treatment, as current off-label options provide minimal relief.

Expanding Haduvio’s Scope

In addition to addressing chronic cough in idiopathic pulmonary fibrosis, Trevi is developing Haduvio for refractory chronic cough (RCC), a condition affecting 2-3 million U.S. adults. RCC often results in significant social and economic burdens, including sleep disruption, urinary incontinence, and psychological distress. Haduvio’s dual action on central and peripheral opioid receptors positions it as a promising solution for both RCC and IPF-related chronic cough.

Looking Ahead

With the CORAL Phase 2b trial progressing as planned and topline results expected in 2025, Trevi Therapeutics remains optimistic about Haduvio’s potential to address critical unmet needs in chronic cough management. While its safety and efficacy are yet to be evaluated by regulatory authorities, the company aims to establish Haduvio as a first-in-class therapy, offering hope to millions of patients worldwide.