Phase 2 Trial of Oral Haduvio to Treat Chronic Cough in IPF Done Enrolling

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by Vanda Pinto, PhD |

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Haduvio| Pulmonary Fibrosis News | illustration of man coughing

Trevi Therapeutics announced that CANAL, its proof-of-concept Phase 2 trial evaluating Haduvio (nalbuphine extended-release tablets) for the treatment of chronic cough in people with idiopathic pulmonary fibrosis (IPF) has finished enrolling.

The trial (NCT04030026), which is taking place in the U.K., has enrolled about 40 IPF patients with chronic cough. According to a recent company press release, sites were notified that they could enroll eligible patients already in screening, but that no additional recruitment was necessary because a statistically significant benefit was recorded in the study’s interim analysis.

Top-line CANAL results on all patients are expected in or before the end of September.

Chronic cough is a common symptom of IPF, a disease characterized by the development of scar tissue in the lungs that interferes with their normal function. Patients with chronic cough have higher rates of depression and anxiety, and fatigue, defined as a state of overwhelming tiredness and lack of energy.

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No therapies are specifically approved to treat cough caused by IPF.

Haduvio is an extended-release tablet formulation of nalbuphine, an approved injectable pain medicine. It works by blocking the mu-opioid receptor, while simultaneously activating the kappa-opioid receptor — two receptors known to be important in the control of coughing and itching.

CANAL is a two-part, placebo-controlled Phase 2 study investigating the safety, tolerability, and efficacy of Haduvio in IPF patients with a persistent cough lasting at least two months.

Initially, patients are randomly assigned to either Haduvio or a placebo for three weeks, followed by a two-week washout period. Then, those treated with the therapy switch to the placebo, while those originally assigned to placebo receive Haduvio for another three weeks.

Treatment-group patients start with a single daily dose of 27 mg of Haduvio, then gradually move over five days to a  54 mg dose taken twice a day. After about four days, this dose then begins to increase over the course of one week until reaching 108 mg taken twice daily. During this period’s final six days, dosing again increases until patients are taking 162 mg of Haduvio twice a day.

The trial’s main goal is to assess changes at week three in mean daytime cough frequency, or coughs per hour, of treated patients relative to those on a placebo using a cough monitor. Changes in coughing frequency on days when patients reach a higher treatment dose (days nine, 16 and 22) will also be evaluated.

A total of 26 patients completed the first three-week treatment period, with the company announcing positive interim analysis results. These people entered the study with a mean daytime cough frequency of 31 coughs per hour.

Data showed that Haduvio reduced cough frequency by 77.4% in treated patients, compared with a 26.7% reduction in those on a placebo, representing a 51.7% drop in coughs per hour.

A 78.1% cough improvement was also observed in all patients during treatment, demonstrated by a 65.9% drop in coughs per hour compared with an increase of 12.2% in patients on a placebo.

Among 18 patients who finished the study’s second part, a 65% cough improvement was reported in those treated compared with a 25.6% cough worsening in those who moved to placebo.

A large proportion (42%) of patients treated with Haduvio experienced a 75% drop in coughs per hour, a finding not seen in any of the participants while on a placebo.

Haduvio was also found to be well generally well tolerated and to have a safety profile consistent with previous studies of nalbuphine extended-release tablets across various health conditions

Trevi also announced it will participate in a webinar, “Understanding the Seriousness of Chronic Cough in IPF Patients and Trevi’s Latest Data,” on March 30, from 8 a.m. to 9 a.m. ET, featuring both company executives and an IPF expert. Online registration is here.

It also plans to take part in two conferences set for this month and next.