Phase 3 trials of Haduvio for chronic cough in IPF expected this year
Results, if positive, would be used to support regulatory approval
Written by |
Trevi Therapeutics plans to launch two pivotal Phase 3 clinical trials to continue testing Haduvio (nalbuphine extended-release) as a treatment for people with idiopathic pulmonary fibrosis (IPF) who have chronic cough.
A pivotal study is one in which results, if positive, are used to support applications for a therapy’s regulatory approval. According to the company, the first trial is expected to start by June, and the second by December.
The trials’ launch follows a positive end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) on the development plan for Haduvio. Besides discussing the launch of the pivotal Phase 3 studies, the FDA also provided feedback on Phase 1 studies that may support a future new drug application seeking approval for the therapy.
“We very much appreciate the FDA’s careful review of our IPF-related chronic cough program to date and the highly collaborative discussions we had during the meeting,” James Cassella, PhD, chief development officer of Trevi, said in a company press release. “We clarified the path forward for our Phase 3 program and received useful guidance on the remaining Phase 1 studies to be conducted. We are well positioned to initiate pivotal parallel Phase 3 trials beginning in the second quarter of 2026 and to execute on the remaining development program.”
Haduvio targets protein receptors that influence cough reflex
IPF, a chronic lung disease of unknown origin, is marked by inflammation that leads to progressive scarring (fibrosis) of lung tissue. As this scar tissue builds up, the lungs become less flexible, making it harder to breathe and often causing symptoms such as persistent cough, breathlessness, and fatigue.
Haduvio is an extended-release form of nalbuphine, given as oral tablets, that works by acting on two protein receptors that influence the cough reflex and related nerve signaling. By modulating these pathways in the brain and the peripheral nervous system, which includes nerves that carry signals between the brain and the rest of the body, the therapy aims to reduce chronic coughing.
In both Phase 3 studies, patients with IPF-related chronic cough will be randomly assigned to receive Haduvio twice daily at a dose of 54 mg or a placebo. In the first trial, about 300 patients are expected to enroll and will be followed for 52 weeks ( one year) of fixed dosing. In the second trial, about 130 patients are expected to enroll and will be followed for 12 weeks (about three months) of fixed dosing.
Our team is focused on advancing Haduvio for these patients and potentially addressing this urgent unmet need.
In both trials, the main goal is to assess the therapy’s efficacy, as measured by changes in 24-hour cough frequency using an objective cough monitor. Trevi noted the protocols are still subject to final FDA review.
“The End-of-Phase 2 meeting was an important milestone for the Company, and we are grateful for the guidance from the FDA. With no FDA-approved therapies for IPF-related chronic cough, it remains highly burdensome for patients living with IPF and is a condition which has historically had limited options,” said Jennifer Good, Trevi’s president and CEO. “Our team is focused on advancing Haduvio for these patients and potentially addressing this urgent unmet need.”
The Phase 3 program follows encouraging signs from earlier studies, namely the Phase 2b CORAL trial (NCT05964335). In this trial, 165 IPF patients with chronic cough were randomly assigned to one of three doses (27 mg, 54 mg, or 108 mg) of Haduvio or a placebo, taken twice daily.
Top-line CORAL results reported that, compared with the placebo, Haduvio reduced daily cough frequency in a dose-dependent manner, including a 36.5% reduction at 54 mg — the dose Trevi plans to use in Phase 3.
