CompletedHeart, Stroke & BloodNIHR-supported projectDigestion, Kidneys & Other Organs
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Reduced Ejection Fraction
Recipient organisationNIHR Wellcome Trust Southampton Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Nov 2025
In plain English
AI plain-English summary
A tablet containing a new drug called tovinontrine is being tested in 12-week clinical trials to see if it lowers a key heart failure marker in the blood. Chronic heart failure with reduced ejection fraction (HFrEF) affects hundreds of thousands of people in the UK, leaving the heart too weak to pump enough blood. Existing treatments help, but many patients still deteriorate. Tovinontrine works by blocking an enzyme called PDE9, which is thought to interfere with the heart’s ability to respond to natural protective signals. This Phase 2 trial will test three doses—2.5 mg, 25 mg, and 50 mg—against a placebo, while patients continue their standard medications. The primary measure is change in NT-proBNP, a blood biomarker that rises when the heart is under strain. If tovinontrine significantly reduces NT-proBNP levels, it would signal that PDE9 inhibition could become a new treatment option for HFrEF. That would mean a potential addition to the limited toolkit doctors have for managing this progressive, life-shortening condition. The trial is not designed to offer immediate benefit to participants, but its results could guide larger Phase 3 studies and, eventually, change how heart failure is treated in routine NHS care.
View original technical description
This is a Phase 2, study to study the safety and efficacy of various doses of tovinontrine in adult patients with chronicHFrEF.The primary endpoint (measurement of what happens to people in the clinical trial) will assess the change in NT-proBNP blood level over 12 weeks compared to placebo. NT-proBNP level in blood is an indicator (biomarker) of effectiveness of the treatment. NT-proBNP has been used as a biomarker in other Phase 2 HF studies, including those testing a drug available on the market called Entresto, working in a similar way in the body as tovinontrine.Tovinontrine clinical drug product is an immediate-release tablet including 2.5 mg, 25 mg, or 50 mg of active drug substance tovinotrine per tablet. The matching placebo (sham medical treatment) tablets are identical in color, size, and shape to the active tablets, and both active and placebo drug product are orally administered, BID.There is a sound scientific and medical rationale for the development of PDE9 inhibitors (such as tovinotrine) for HF. Nevertheless, there may not be any clinical benefit from taking part in this research study. However, the results of this research will benefit science and may guide the future treatment of patients with HF.The study will include a placebo arm (sham treatment). A placebo arm is considered necessary because NT-proBNP may change during the course of the study without additional drug intervention, and therefore, an objective comparison of the effect of each tovinontrine dose level with placebo-treated patients is necessary. Further, to ensure adequate treatment for study patients, standard-of-care medications for HF treatment are not excluded during study participation.Taking into account the measures taken to mitigate risk to patients in this study, the potential risks identified in association with tovinontrine are justified by the anticipated potential benefits that may be afforded to patients with HFrEF.
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