Trevi Therapeutics (TRVI) Study Result summary

Study Design and Objectives

• The Phase II-A RIVER trial was a randomized, double-blind, placebo-controlled, two-period crossover study evaluating Haduvio (oral nalbuphine ER) in refractory chronic cough (RCC) patients, enrolling 66 participants with 59 included in the primary efficacy analysis.

• Patients were stratified by baseline cough frequency and received escalating doses (27 mg, 54 mg, 108 mg BID) or placebo for 21 days, with a 21-day washout and crossover; objective cough assessments were performed at each dose.

• The primary endpoint was the relative change from baseline in 24-hour cough frequency at Day 21, measured objectively using the VitaloJAK device.

• Secondary endpoints included patient-reported cough frequency, cough severity (CS-VAS), and quality of life measures.

• The study population had a mean age of 60.2 years, with 66.7% female and 92.4% white.

Efficacy Results

• Haduvio achieved a 67% reduction in 24-hour cough frequency from baseline and a 57% placebo-adjusted reduction (p<0.0001), with efficacy observed as early as Day 7 at the lowest dose.

• Statistically significant reductions were consistent across both moderate (10–19 coughs/hr) and severe (≥20 coughs/hr) subgroups, with 68% and 66% reductions, respectively.

• 84% of patients achieved at least a 30% reduction in cough frequency, and 77% achieved at least a 50% reduction.

• Patient-reported outcomes, including cough severity and frequency, showed significant improvements corroborating objective findings.

• Haduvio is the first therapy to show significant reduction in chronic cough across both RCC and IPF patients.

Safety and Tolerability

• No treatment-emergent serious adverse events were reported; safety profile was consistent with prior studies and most adverse events were mild to moderate.

• Most common adverse events (≥10%) were constipation (28.6%), somnolence (25.4%), nausea (22.2%), dizziness (19.0%), headache (15.9%), and fatigue (14.3%).

• Six patients experienced Grade 3 adverse events, but none exceeded this severity.

• Discontinuation due to adverse events was 14.3–15%, with no serious adverse events reported.