Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Preserved Ejection Fraction (Cycle-2-PEF) (Cycle-2-PEF)

November 13, 2025 updated by: Cardurion Pharmaceuticals, Inc.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Preserved Ejection Fraction

The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with preserved ejection fraction

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

303

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Chermside, Australia
        • Cardurion Investigative Site
  • Belgium
      • Bruges, Belgium, 8000
        • Cardurion Investigative Site
      • Sint-Niklaas, Belgium, 9100
        • Cardurion Investigative Site
  • Bulgaria
      • Burgas, Bulgaria, 8008
        • Cardurion Investigative Site
      • Gabrovo, Bulgaria, 5300
        • Cardurion Investigative Site
      • Plovdiv, Bulgaria, 4002
        • Cardurion Investigative Site
      • Plovdiv, Bulgaria, 4003
        • Cardurion Investigative Site
      • Rousse, Bulgaria, 7000
        • Cardurion Investigative Site
      • Sofia, Bulgaria, 1000
        • Cardurion Investigative Site
      • Stara Zagora, Bulgaria, 6000
        • Cardurion Investigative Site
  • Canada
    • Ontario
      • Cambridge, Ontario, Canada, N1R 6V6
        • Cardurion Investigative Site
      • Hamilton, Ontario, Canada, L8L 2X2
        • Cardurion Investigative Site
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Cardurion Investigative Site
      • Montreal, Quebec, Canada
        • Cardurion Investigative Site
      • Sherbrooke, Quebec, Canada, J1G 2E8
        • Cardurion Investigative Site
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Cardurion Investigative Site
  • Czechia
      • Hradec Králové, Czechia, 500 02
        • Cardurion Investigative Site
      • Hradec Králové, Czechia, 50005
        • Cardurion Investigative Site
      • Prague, Czechia, 128 02
        • Cardurion Investigative Site
  • Germany
      • Dresden, Germany, 01067
        • Cardurion Investigational Site
      • Magdeburg, Germany, 39120
        • Cardurion Investigative Site
    • Brandenburg
      • Elsterwerda, Brandenburg, Germany, 04910
        • Cardurion Investigative Site
    • Lower Saxony
      • Papenburg, Lower Saxony, Germany, 26871
        • Cardurion Investigative Site
    • State of Berlin
      • Brandenburg, State of Berlin, Germany, 10787
        • Cardurion Investigative Site
  • Hungary
      • Balatonfüred, Hungary, 8230
        • Cardurion Investigative Site
      • Budapest, Hungary, H-1122
        • Cardurion Investigative Site
      • Gyöngyös, Hungary, 3200
        • Cardurion Investigative Site
      • Hatvan, Hungary, 3000
        • Cardurion Investigative Site
      • Orosháza, Hungary, 5900
        • Cardurion Investigative Site
  • Italy
      • Milan, Italy, 20138
        • Cardurion Investigative Site
  • Netherlands
      • Eindhoven, Netherlands, 5504 DL
        • Cardurion Investigative Site
      • Groningen, Netherlands, 9713 AP
        • Cardurion Investigative Site
      • Hardenberg, Netherlands, 7772 SE
        • Cardurion Investigative Site
      • Sneek, Netherlands, 8601 ZR
        • Cardurion Investigative Site
      • Zutphen, Netherlands, 7207 AE
        • Cardurion Investigative Site
  • New Zealand
      • Dunedin, New Zealand
        • Cardurion Investigative Site
  • Poland
      • Grodzisk Mazowiecki, Poland, 05-825
        • Cardurion Investigative Site
      • Lodz, Poland, 92-213
        • Cardurion Investigative Site
      • Lublin, Poland, 20-011
        • Cardurion Investigative Site
      • Sopot, Poland, 81-717
        • Cardurion Investigative Site
      • Torun, Poland, 87-100
        • Cardurion Investigative Site
      • Warsaw, Poland
        • Cardurion Investigative Site
      • Wroclaw, Poland, 50-556
        • Cardurion Investigative Site
      • Wroclaw, Poland, 50-981
        • Cardurion Investigative Site
  • Spain
      • Córdoba, Spain, 14004
        • Cardurion Investigative Site
      • Málaga, Spain, 29010
        • Cardurion Investigative Site
      • Santiago de Compostela, Spain, 15706
        • Cardurion Investigative Site
      • Seville, Spain, 41009
        • Cardurion Investigative Site
      • Valencia, Spain, 46026
        • Cardurion Investigative Site
  • Taiwan
      • Kaohsiung City, Taiwan
        • Cardurion Investigative Site
      • Taipei, Taiwan
        • Cardurion Investigative Site
      • Taipei County, Taiwan
        • Cardurion Investigative Site
      • Taoyuan District, Taiwan
        • Cardurion Investigative Site
  • United Kingdom
      • Bridgend, United Kingdom, CF31 1RQ
        • Cardurion Investigative Site
      • Chichester, United Kingdom, PO19 6SE
        • Cardurion Investigative Site
      • Dundee, United Kingdom, DD1 9SY
        • Cardurion Investigative Site
      • Glasgow, United Kingdom, G81 4DY
        • Cardurion Investigative Site
      • Harrow, United Kingdom, HA1 3UJ
        • Cardurion Investigative Site
      • Isleworth, United Kingdom, TW7 6AF
        • Cardurion Investigative Site
      • London, United Kingdom, SE5 9RS
        • Cardurion Investigative Site
      • London, United Kingdom, W1T 7HA
        • Cardurion Investigative Site
      • Southampton, United Kingdom, SO16 6YD
        • Cardurion Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Cardurion Investigative Site
    • Arkansas
      • Little Rock, Arkansas, United States, 72204
        • Cardurion Investigative Site
    • California
      • Orange, California, United States, 92868
        • Cardurion Investigative Site
      • Torrance, California, United States, 90502
        • Cardurion Investigative Site
      • Van Nuys, California, United States, 91405
        • Cardurion Investigative Site
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Cardurion Investigative Site
      • Miami, Florida, United States, 33137
        • Cardurion Investigative Site
    • Illinois
      • Hazel Crest, Illinois, United States, 60429
        • Cardurion Investigative Site
      • Peoria, Illinois, United States, 61636
        • Cardurion Investigative Site
    • Louisiana
      • Alexandria, Louisiana, United States, 71301
        • Cardurion Investigative Site
      • Covington, Louisiana, United States, 70433
        • Cardurion Investigative Site
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Cardurion Investigative Site
    • New York
      • Buffalo, New York, United States, 14215
        • Cardurion Investigative Site
      • New York, New York, United States, 10019
        • Cardurion Investigative Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cardurion Investigative Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73135
        • Cardurion Investigative Site
    • Oregon
      • Portland, Oregon, United States, 97225
        • Cardurion Investigative Site
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Cardurion Investigative Site
    • Tennessee
      • Nashville, Tennessee, United States, 37232-7601
        • Cardurion Investigative Site
    • Texas
      • Dallas, Texas, United States, 75246
        • Cardurion Investigative Site
      • McKinney, Texas, United States, 75069
        • Cardurion Investigative Site
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Cardurion Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Is an adult male or female patient ≥ 18 years of age

  • Has evidence in the medical history supporting a diagnosis of clinical HF syndrome, NYHA functional class II to III, with the duration of at least 6 months prior to the time of Screening. The HF syndrome is defined by documentation of 1 or more of the following:

    • At least 1 of the typical symptoms due to HF such as dyspnea and/or fatigue limiting exercise capacity;
    • At least 1 of the typical signs of HF such as peripheral edema, elevated jugular venous pressure, pulmonary crackles; or
    • Hospitalization, emergency department visit, or outpatient visit for HF requiring intravenous (IV) or subcutaneous (SQ) diuresis within the past 12 months.
  • Has ejection fraction (EF) >40% and left atrial enlargement by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening;
  • Has NT-proBNP level ≥ 300 pg/mL at the time of Screening. Patients with atrial fibrillation or flutter at the time of Screening are required to have an NT proBNP level of ≥500 pg/mL at the time of Screening;
  • Is on stable optimized doses of guideline-directed HF therapy, per Investigator's clinical judgment, for a minimum of 4 weeks prior to the time of Screening and during the Screening Period, with no planned changes after randomization; Has had no addition of new guideline-directed HF therapy within the 3 months prior to the time of Screening or during the Screening Period;

Exclusion Criteria:

  • Has documented EF ≥ 60% by TTE within 6 months of the time of Screening or during the Screening Period;
  • Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 60 days of the time of Screening or during the Screening Period;
  • Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration;
  • Has elective interventions (eg, percutaneous coronary intervention, device implantations, percutaneous structural heart disease interventions, cardiac and non-cardiac surgery) planned to occur during involvement in this study;
  • Has acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, or carotid angioplasty within 60 days of the time of Screening or during the Screening Period;
  • Has had a prior or planned orthotopic heart transplantation;
  • Has presence of or plan for mechanical circulatory support;

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Tablets administered orally
Experimental: Tovinontrine (CRD-750)
Drug: Tovinontrine (CRD-750
Tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in biomarkers from Baseline to Week 12 - NT-proBNP
Time Frame: Baseline to Week 12
The percent change in plasma NT-proBNP from Baseline to Week 12.
Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in biomarkers at week 12 by treatment group - cGMP
Time Frame: Baseline to Week 12
The percent change in urine and plasma cGMP from Baseline to Week 12.
Baseline to Week 12
Change in biomarkers at week 12 by treatment group - BNP
Time Frame: Baseline to Week 12
The percent change in BNP from Baseline to Week 12.
Baseline to Week 12
Change in the biomarker ratio at Week 12 - NT-proBNP
Time Frame: Baseline to Week 12
The percent change in the urine and plasma cGMP to NT-proBNP ratio at week 12.
Baseline to Week 12
Change in the biomarker ratio at Week 12 - BNP
Time Frame: Baseline to Week 12
The percent change in the urine and plasma cGMP to BNP ratio from Baseline to Week 12.
Baseline to Week 12
The change from baseline in the KCCQ-23-CSS
Time Frame: Baseline to Week 12
The proportion of patients with a ≥5, 10, and 20-point improvement in the KCCQ-23-CSS at Week 12
Baseline to Week 12
New York Heart Association (NYHA) classification at Week 12
Time Frame: Week 12
The post-baseline NYHA classification at Week 12
Week 12
Treatment Emergent Adverse Events (TEAEs)
Time Frame: Baseline to Week 12
The number of participants with TEAEs including drug related AEs, serious AEs (SAEs), and AEs leading to study drug discontinuation.
Baseline to Week 12
The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23)
Time Frame: Baseline to Week 12
Scaled 0 to 100 where lower scores represent worse health status than higher scores
Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardurion Pharmaceuticals, Inc.

Investigators

  • Study Director: Gail Berman, Senior VP Head, Clinical Development Cardurion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2024

Primary Completion (Actual)

September 2, 2025

Study Completion (Actual)

September 2, 2025

Study Registration Dates

First Submitted

December 13, 2023

First Submitted That Met QC Criteria

January 19, 2024

First Posted (Actual)

January 22, 2024

Study Record Updates

Last Update Posted (Actual)

November 17, 2025

Last Update Submitted That Met QC Criteria

November 13, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRD-750-202
  • 2023-508737-13 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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