Phase 2 Trial of Haduvio for Chronic Cough Due to IPF Again Enrolling in UK

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by Teresa Carvalho, MS |

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Haduvio trial reopens

A Phase 2 study of Haduvio (nalbuphine extended release tablets) to treat chronic cough in people with idiopathic pulmonary fibrosis (IPF) is again enrolling eligible patients, Trevi Therapeutics, the therapy’s developer, announced.

The U.K. trial was placed on hold due to the COVID-19 pandemic, as IPF patients are among at-risk groups for the disease.

“I am pleased to see Trevi’s trial for chronic cough in IPF patients restart screening after pausing due to the COVID-19 pandemic,” Toby Maher, MD, the trial’s lead investigator, said in a press release.

“IPF is a debilitating disease, with chronic cough being a significant contributor to a patient’s reduced quality of life. Nalbuphine ER [extended release] is of particular interest for the clinical treatment of chronic cough due to the potential of its mixed agonist/antagonist mechanism of action,” Maher added.

Persistent cough is a common symptom of IPF, affecting patients’ general health and life quality. No specific therapies are approved to treat cough due to pulmonary fibrosis.

Haduvio acts by blocking (an antagonist) the mu-opioid receptor, while it activates (an agonist) the kappa-opioid receptor. These receptors are thought to be crucial in the control of breathing, cough, and itching.

The Phase 2 trial (NCT04030026) is a two-part, placebo-controlled study testing Haduvio’s safety, tolerability, and efficacy of in up to 60 IPF patients, ages 18 to 80, with chronic cough for at least two months. Enrollment is, or soon will be, taking place at sites across the United Kingdom; additional information can be found here.

Patients will be randomized to either daily Haduvio or a placebo for three weeks, followed by a two-week washout period. Those who were on the treatment in the study’s first part will then move to placebo, while those on placebo will now be given Haduvio for another three weeks.

A single daily dose of 27 mg of Haduvio, in tablet form, is first given to participants, increasing to a twice-a-day dose of 54 mg over five days. This dose will be maintained for about four days, then will successively increase over one week until reaching 108 mg twice daily. It will then increase over six days to 162 mg taken twice a day.

The trial’s primary goal to evaluate changes in mean cough frequency, or coughs per hour, when the person is awake. A cough monitor will be used. Secondary goals include changes in daytime cough frequency with increasing treatment doses.

Due to the ongoing pandemic, the study’s protocol was revised to require fewer in-person visits and fewer procedures, said Thomas Sciascia, MD, Trevi’s chief medical officer. These changes were approved by the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA).

To accelerate trial enrollment and minimize the COVID-related risks of a single country study, the company is considering opening sites in Germany.

Haduvio is also being tested as a potential treatment for chronic pruritus. A Phase 2b/3 clinical trial of Haduvio in people with severe pruritus associated with prurigo nodularis (PN), a skin disease that causes hard, itchy lumps, is underway.

“We have seen continued momentum in the enrollment in the PN trial and look forward to helping the remaining clinical sites for cough in IPF get restarted,” said Jennifer L. Good, president and CEO of Trevi Therapeutics. “We are pleased with the continued progress of our clinical development programs in these two severe conditions.”

Nalbuphine is approved in the U.S. and Europe as an injectable treatment of moderate to severe pain.

The oral formulation of this therapy is also being evaluated as a possible treatment for levodopa-induced dyskinesia in people with Parkinson’s disease. Due to how nalbuphine works to modulate opioid receptors in the nervous system, the company thinks it can be effective in treating symptoms of these three diseases.

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