First global trial now testing new treatment for chronic cough in IPF
US enrollment opens for 1 of 2 pivotal studies of extended-release oral therapy
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According to its U.S. developer, the first of two global clinical trials designed to test Haduvio (nalbuphine extended-release) — a potential treatment for chronic cough due to idiopathic pulmonary fibrosis (IPF) — is now underway, with the second expected to launch later this year.
The initial Phase 3 trial, dubbed OCEAN-1 (NCT07671911), is evaluating the safety and effectiveness of Haduvio versus a placebo over one year in about 300 adults at sites around the world. Recruitment of IPF patients ages 40 and older with cough lasting at least eight weeks, or about two months, is now ongoing at five sites in the U.S.
Top-line data, or early key results, on the use of the oral treatment are expected in the first half of 2028.
“With no … approved therapies currently available, Haduvio has the potential to become a first-in-class therapy that makes a meaningful difference in patients’ lives,” Jennifer Good, president and CEO of Trevi Therapeutics, the therapy’s developer, said in a company press release providing financial results and business updates.
“We are on track with our clinical trial plans as we initiated our first Phase 3 trial of Haduvio in patients with IPF-related chronic cough,” Good said, adding that the second late-stage trial should be underway by the end of September.
That parallel Phase 3 trial, called OCEAN-2, will be smaller and shorter. It’s expected to enroll approximately 130 participants with IPF-related chronic cough, assessing changes after 12 weeks, or about three months, of treatment. Top-line data from that trial are expected in the second half of 2027, the release stated.
Both OCEAN-1 and OCEAN-2 are pivotal trials, meaning they are designed to provide robust evidence that, if positive, can support an application seeking the therapy’s regulatory approval.
The plans to launch these trials followed an end-of-Phase 2 meeting with the U.S. Food and Drug Administration, during which Trevi and the regulatory agency agreed on key aspects of the two Phase 3 trials.
No treatments are approved for IPF-related chronic cough
IPF is a chronic, progressive lung disease of unknown cause in which scar tissue, known as fibrosis, builds up in the lungs. As this scar tissue accumulates, the lungs become increasingly stiff, making breathing more difficult and leading to symptoms such as shortness of breath, fatigue, and a persistent dry cough.
Chronic cough is particularly common in people with IPF and can substantially affect quality of life, data have shown. According to Trevi, about two-thirds of the approximately 140,000 people living with IPF in the U.S. experience uncontrolled chronic cough, with some individuals coughing as many as 1,500 times per day. Yet, there are no treatments specifically approved for IPF-related chronic cough.
Haduvio is an extended-release formulation of nalbuphine, a molecule that acts on two protein receptors in the brain and nerves outside the brain and spinal cord that are involved in regulating the cough reflex. By modulating these pathways, Haduvio, available as oral tablets, is expected to reduce chronic coughing.
Both OCEAN-1 and OCEAN-2 are randomized, double-blind, placebo-controlled trials, meaning participants will be randomly assigned to receive either Haduvio or a placebo, and neither patients nor the investigators will know who is getting which one.
The two studies will assess whether the therapy is superior to the placebo at reducing 24-hour cough frequency, measured with an objective cough monitor, as their main goal.
In OCEAN-1, participants will receive Haduvio at 54 mg or a placebo, twice daily for 52 weeks, or about one year. Those taking approved antifibrotic medications, which are used to slow the progression of lung scarring, may continue treatment if they have been on a stable dose for at least six weeks.
The trial’s main goal is to determine whether Haduvio reduces 24-hour cough frequency after 26 weeks, or about six months, compared with the placebo. Secondary goals include absolute changes in cough severity over time, the proportion of participants achieving substantial reductions in cough frequency, and changes in breathlessness. The researchers will also track other respiratory symptoms and cough-related quality of life.
Throughout the study, the therapy’s safety and tolerability will also be monitored.
OCEAN-2 will test the same 54 mg twice-daily dose against a placebo but for only 12 weeks. Further details about the study’s design have not yet been disclosed.
New trials build on findings of earlier study of Haduvio
The Phase 3 program builds on findings from the Phase 2b CORAL trial (NCT05964335), which tested three doses of Haduvio — 27 mg, 54 mg, and 108 mg — versus the placebo in 165 people with IPF-related chronic cough. All doses were taken twice daily for six weeks,
Top-line results showed that Haduvio reduced daily cough frequency in a dose-dependent manner. At 54 mg twice daily — the dose selected for both Phase 3 trials — Haduvio reduced cough frequency by 36.5% relative to the placebo. The therapy also significantly reduced cough severity by the six-week mark, and eased the impact of coughing on patients’ daily lives.
Discontinuation rates due to adverse events were similar with Haduvio and the placebo (5.6% vs. 5%), with the most common events being mild to moderate in severity.
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