Trevi Therapeutics Announces Positive Outcome from Sample Size Re-estimation Resulting in No Change to the Current Sample Size for the Phase 2b CORAL Trial in Idiopathic Pulmonary Fibrosis Patients with Chronic Cough

Rhea-AI Summary

Trevi Therapeutics (NASDAQ: TRVI) announced positive results from its planned sample size re-estimation (SSRE) for the Phase 2b CORAL trial, confirming no changes needed to the current sample size of 160 patients. The trial, testing Haduvio™ for chronic cough in idiopathic pulmonary fibrosis (IPF) patients, has reached 75% enrollment, with topline results expected in H1 2025.

The SSRE analysis, conducted on the highest dose (108mg twice daily) after 80 patients completed treatment, supported maintaining the pre-specified conditional power of 80% or greater. The CORAL trial is evaluating three doses of Haduvio (27mg, 54mg, and 108mg twice daily) against placebo in IPF patients with chronic cough, with the primary endpoint measuring relative change in 24-hour cough frequency.

Positive

• Trial reached 75% enrollment milestone
• SSRE analysis confirms original trial design adequacy
• No need for sample size increase, potentially saving time and resources
• Trial maintains strong statistical power (80% or greater)

Negative

• Results not expected until first half of 2025
• Still requires completion of remaining 25% enrollment

Insights

Medical Research Analyst

The SSRE outcome for Trevi's Phase 2b CORAL trial is significantly positive, confirming the statistical power of the original trial design with N=160 patients. The maintenance of the initial sample size, rather than requiring an increase, suggests strong preliminary efficacy signals that align with the positive Phase 2a results. With 75% enrollment achieved and the highest dose (108mg BID) showing promising data at the interim analysis, the trial maintains its statistical integrity and timeline for topline results in H1 2025. The study's robust design, including objective cough monitoring via VitaloJAK® and multiple dose arms, positions it well to demonstrate clinical significance. For IPF patients with chronic cough, an area with no approved treatments, these developments strengthen Haduvio's potential as a first-in-class therapy.

Financial Analyst

This development significantly derisks Trevi's lead program by validating the trial design and potentially reducing development costs by avoiding sample size expansion. With a market cap of $194.4M, positive SSRE data could attract strategic partnerships or additional institutional investment interest. The confirmation of the original trial size suggests strong preliminary efficacy, which could accelerate the path to market for Haduvio in a currently untapped indication. The maintained timeline for H1 2025 topline results provides clear near-term catalysts for investors. The first-mover advantage in IPF chronic cough represents substantial commercial potential, particularly given the lack of approved therapies in this space.

Independent Data Monitoring Statistician reaffirmed current sample size to remain at N=160

The trial has reached 75% of the targeted enrollment, and topline results continue to be expected in the first half of 2025

NEW HAVEN, Conn., Dec. 12, 2024 /PRNewswire/ -- Trevi Therapeutics, Inc. (Nasdaq: TRVI), a clinical-stage biopharmaceutical company developing the investigational therapy Haduvio™ (oral nalbuphine ER) for the treatment of patients with chronic cough in idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC), today announced the positive outcome from the planned sample size re-estimation (SSRE) for the ongoing Phase 2b CORAL trial in IPF patients with chronic cough, which requires no change to the current sample size for the trial (N=160). The trial has reached 75% of the targeted enrollment, and topline results from the full trial continue to be expected in the first half of 2025.

The SSRE analysis was conducted on the highest dose (108mg twice daily) in the trial after 50% of the initial targeted trial enrollment, or 80 patients, completed the six weeks of treatment. Based on the SSRE analysis, it was recommended that the CORAL trial should continue as planned to maintain the pre-specified conditional power of 80% or greater. The other two potential pre-specified outcomes of the SSRE analysis were an increase in the sample size or futility.

"We are pleased that the SSRE outcome supports the continued execution of the CORAL trial with the total number of patients as originally planned," said Jennifer Good, President and CEO of Trevi Therapeutics. "This positive SSRE outcome is reassuring and confirms the key powering assumptions of the trial design. We believe this is additional confirmation of the strong efficacy observed in the Phase 2a CANAL trial in IPF cough and is an important milestone reaffirming our belief in Haduvio's best-in-class and first-in-class potential for patients with IPF chronic cough where there are no approved therapies."

Phase 2b IPF Chronic Cough Trial Design (CORAL):
The CORAL trial is a double-blind, randomized, placebo-controlled, parallel-arm trial evaluating three doses of Haduvio (27mg, 54mg, and 108mg twice daily) compared to placebo in IPF patients with chronic cough. Approximately 160 IPF patients with chronic cough will be randomized 1:1:1:1 to one of three Haduvio doses or placebo for a period of 6 weeks. This includes an initial 2-week titration period to the target dose followed by 4 weeks of fixed dosing. The primary efficacy endpoint for the trial is the relative change in 24-hour cough frequency at the end of Week 6 versus baseline for Haduvio compared to placebo, as measured with an objective cough monitor (VitaloJAK®). The trial will also explore secondary endpoints, including patient reported outcome measures for cough.

About Trevi Therapeutics, Inc.
Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing the investigational therapy Haduvio™ (oral nalbuphine extended-release) for the treatment of chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC). Haduvio acts on the cough reflex arc both centrally and peripherally as a kappa agonist and a mu antagonist (KAMA), which are opioid receptors that play a key role in controlling cough hypersensitivity. Nalbuphine is not currently scheduled by the U.S. Drug Enforcement Agency.  

Chronic cough is a highly prevalent disease in IPF patients, impacting up to 85% of the IPF population. There are ~140,000 U.S. IPF patients and the impact of chronic cough is significant with patients coughing up to 1,500 times per day. This consistent cough and associated damage may lead to worsening disease, a higher risk of progression, death, or need for lung transplant. Chronic cough also often leads to a decline in patients' social, physical, and psychological quality of life. There are no approved therapies for the treatment of chronic cough in IPF and current off-label treatment options provide minimal benefit to patients. 

Refractory chronic cough affects approximately 2-3 million adults in the U.S. and is caused by cough reflex hypersensitivity in both the central and peripheral nerves. It is highly disruptive and accompanied by a wide range of complications, ranging from urinary incontinence in females to sleep disruption and social embarrassment that causes significant social and economic burdens for patients and those around them. Haduvio is being developed for the treatment of moderate to severe RCC. There are also no approved therapies for RCC in the U.S.  

Trevi intends to propose Haduvio as the trade name for oral nalbuphine ER. Its safety and efficacy have not been evaluated by any regulatory authority.  

For more information, visit www.TreviTherapeutics.com and follow Trevi on X (formerly Twitter) and LinkedIn.  

Forward-Looking Statements 
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding Trevi's business plans and objectives, including future plans or expectations for Haduvio and plans and timing with respect to clinical trials and clinical data, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions. Risks that contribute to the uncertain nature of the forward-looking statements include: uncertainties regarding the success, cost and timing of Trevi's product candidate development activities and ongoing clinical trials; the risk that positive data from a clinical trial, or from the sample size re-estimation analysis announced in this press release, may not necessarily be predictive of the results of later clinical trials in the same or a different indication; uncertainties regarding Trevi's ability to execute on its strategy; uncertainties with respect to regulatory authorities' views as to the data from Trevi's clinical trials and next steps in the development path for Haduvio in the United States and foreign countries,  as well as other risks and uncertainties set forth in Trevi's quarterly report on Form 10-Q for the quarter ended September 30, 2024 filed with the Securities and Exchange Commission and in subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Trevi undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Investor Contact
Katie Barrett
Trevi Therapeutics, Inc.
203-304-2499
k.barrett@trevitherapeutics.com

Media Contact
Rosalia Scampoli
914-815-1465
rscampoli@marketcompr.com

 

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SOURCE Trevi Therapeutics, Inc.

FAQ

What were the results of TRVI's Phase 2b CORAL trial sample size re-estimation?

The SSRE analysis confirmed no changes were needed to the current sample size of 160 patients, maintaining the pre-specified conditional power of 80% or greater.

When will Trevi Therapeutics (TRVI) release CORAL trial topline results?

Topline results from the full Phase 2b CORAL trial are expected in the first half of 2025.

What doses of Haduvio are being tested in TRVI's CORAL trial?

The trial is evaluating three doses of Haduvio: 27mg, 54mg, and 108mg twice daily, compared to placebo.

What is the primary endpoint of TRVI's Phase 2b CORAL trial?

The primary endpoint is the relative change in 24-hour cough frequency at Week 6 versus baseline for Haduvio compared to placebo, measured using VitaloJAK® cough monitor.

How many patients have been enrolled in TRVI's CORAL trial as of December 2023?

The trial has reached 75% of the targeted enrollment of 160 patients.