Trevi Therapeutics has announced that its Phase 2b CORAL trial, investigating Haduvio (nalbuphine extended-release tablets) for chronic cough in patients with idiopathic pulmonary fibrosis (IPF), has achieved 75% of its targeted enrollment. This milestone brings the trial closer to completion, with top-line data expected in the first half of 2025. The CORAL trial aims to evaluate the efficacy and safety of Haduvio in addressing the unmet need for effective cough treatments in IPF patients.
CORAL Trial Design and Objectives
The Phase 2b CORAL trial (NCT05964335) is actively recruiting a total of 160 patients across multiple sites in 10 countries, including Australia, Canada, Chile, Turkey, and several European nations. Participants are randomized to receive one of three doses of Haduvio (27, 54, or 108 mg) or a placebo, administered twice daily for six weeks. The primary endpoint of the study is to assess changes in 24-hour cough frequency. Secondary endpoints include patient-reported outcomes related to cough severity, breathlessness, and overall quality of life.
An independent sample size re-estimation analysis, conducted after half of the participants in the highest dose group completed six weeks of treatment, supported the continuation of the trial with the originally planned sample size. This analysis indicated an 80% or higher likelihood of generating statistically significant data.
Haduvio: A Novel Approach to Cough Management in IPF
Haduvio is an oral extended-release formulation of nalbuphine, a compound that modulates the activity of protein receptors involved in nerve-signaling pathways that mediate coughing. It acts on nerves within the central and peripheral nervous systems. IPF is a chronic and progressive lung disease characterized by inflammation and tissue scarring (fibrosis) in the lungs, leading to symptoms such as chronic cough, shortness of breath, and fatigue. Currently, there are no approved therapies specifically targeting chronic cough in IPF patients.
Promising Results from Previous Phase 2a Trial
Prior to the CORAL trial, a Phase 2a trial (NCT04030026), known as CANAL, demonstrated that Haduvio significantly reduced coughing in IPF patients. Data from the CANAL trial showed a 75.1% reduction in daytime cough frequency with Haduvio compared to a 22.6% reduction with placebo. Similar results were observed for 24-hour cough frequency, with a 76.1% reduction in the Haduvio group versus a 25.3% reduction in the placebo group.
Jennifer Good, Trevi’s president and CEO, stated that the positive outcome from the sample size re-estimation confirms the key powering assumptions of the trial design. She also noted that this milestone reaffirms their belief in Haduvio’s potential as a best-in-class and first-in-class treatment for IPF-related chronic cough, where no approved therapies currently exist. Good added that the analysis provides additional confirmation of the strong efficacy observed in the Phase 2a CANAL trial.
