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

NCT06215586 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CRD-750-2022023-508737-13
• Study Type: interventional
• Target: 303
• Locations: 15 countries
• Sites: 84

Brief Summary

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

Conditions

Heart Failure; Heart Failure Preserved Ejection Fraction; Cardiovascular Diseases; Heart Diseases

Keywords

PDE9; PED9 Inhibitor; Heart Failure; CRD-750; Tovinontrine; HFpEF

Outcome Measures

Primary Outcomes (1)

• Change in biomarkers from Baseline to Week 12 - NT-proBNP

  The percent change in plasma NT-proBNP from Baseline to Week 12.

  Baseline to Week 12

Secondary Outcomes (8)

• Change in biomarkers at week 12 by treatment group - cGMP

  Baseline to Week 12

• Change in biomarkers at week 12 by treatment group - BNP

  Baseline to Week 12

• Change in the biomarker ratio at Week 12 - NT-proBNP

  Baseline to Week 12

• Change in the biomarker ratio at Week 12 - BNP

  Baseline to Week 12

• The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23)

  Baseline to Week 12

Study Arms (2)

Tovinontrine (CRD-750)

EXPERIMENTAL

Drug: Tovinontrine (CRD-750

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tovinontrine (CRD-750 DRUG

Tablets administered orally

Tovinontrine (CRD-750)

Placebo DRUG

Tablets administered orally

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Cardurion Pharmaceuticals, Inc.: lead

Study Sites (84)

Cardurion Investigative Site

Birmingham, Alabama, 35233, United States

Location

Cardurion Investigative Site

Little Rock, Arkansas, 72204, United States

Location

Cardurion Investigative Site

Orange, California, 92868, United States

Location

Cardurion Investigative Site

Torrance, California, 90502, United States

Location

Cardurion Investigative Site

Van Nuys, California, 91405, United States

Location

Cardurion Investigative Site

Jacksonville, Florida, 32216, United States

Location

Cardurion Investigative Site

Miami, Florida, 33137, United States

Location

Cardurion Investigative Site

Hazel Crest, Illinois, 60429, United States

Location

Cardurion Investigative Site

Peoria, Illinois, 61636, United States

Location

Cardurion Investigative Site

Alexandria, Louisiana, 71301, United States

Location

Cardurion Investigative Site

Covington, Louisiana, 70433, United States

Location

Cardurion Investigative Site

St Louis, Missouri, 63110, United States

Location

Cardurion Investigative Site

Buffalo, New York, 14215, United States

Location

Cardurion Investigative Site

New York, New York, 10019, United States

Location

Cardurion Investigative Site

Cleveland, Ohio, 44195, United States

Location

Cardurion Investigative Site

Oklahoma City, Oklahoma, 73135, United States

Location

Cardurion Investigative Site

Portland, Oregon, 97225, United States

Location

Cardurion Investigative Site

Rapid City, South Dakota, 57701, United States

Location

Cardurion Investigative Site

Nashville, Tennessee, 37232-7601, United States

Location

Cardurion Investigative Site

Dallas, Texas, 75246, United States

Location

Cardurion Investigative Site

McKinney, Texas, 75069, United States

Location

Cardurion Investigative Site

Burlington, Vermont, 05401, United States

Location

Cardurion Investigative Site

Chermside, Australia

Location

Cardurion Investigative Site

Bruges, 8000, Belgium

Location

Cardurion Investigative Site

Sint-Niklaas, 9100, Belgium

Location

Cardurion Investigative Site

Burgas, 8008, Bulgaria

Location

Cardurion Investigative Site

Gabrovo, 5300, Bulgaria

Location

Cardurion Investigative Site

Plovdiv, 4002, Bulgaria

Location

Cardurion Investigative Site

Plovdiv, 4003, Bulgaria

Location

Cardurion Investigative Site

Rousse, 7000, Bulgaria

Location

Cardurion Investigative Site

Sofia, 1000, Bulgaria

Location

Cardurion Investigative Site

Stara Zagora, 6000, Bulgaria

Location

Cardurion Investigative Site

Cambridge, Ontario, N1R 6V6, Canada

Location

Cardurion Investigative Site

Hamilton, Ontario, L8L 2X2, Canada

Location

Cardurion Investigative Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Cardurion Investigative Site

Montreal, Quebec, Canada

Location

Cardurion Investigative Site

Sherbrooke, Quebec, J1G 2E8, Canada

Location

Cardurion Investigative Site

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Cardurion Investigative Site

Hradec Králové, 500 02, Czechia

Location

Cardurion Investigative Site

Hradec Králové, 50005, Czechia

Location

Cardurion Investigative Site

Prague, 128 02, Czechia

Location

Cardurion Investigative Site

Elsterwerda, Brandenburg, 04910, Germany

Location

Cardurion Investigative Site

Papenburg, Lower Saxony, 26871, Germany

Location

Cardurion Investigative Site

Brandenburg, State of Berlin, 10787, Germany

Location

Cardurion Investigational Site

Dresden, 01067, Germany

Location

Cardurion Investigative Site

Magdeburg, 39120, Germany

Location

Cardurion Investigative Site

Balatonfüred, 8230, Hungary

Location

Cardurion Investigative Site

Budapest, H-1122, Hungary

Location

Cardurion Investigative Site

Gyöngyös, 3200, Hungary

Location

Cardurion Investigative Site

Hatvan, 3000, Hungary

Location

Cardurion Investigative Site

Orosháza, 5900, Hungary

Location

Cardurion Investigative Site

Milan, 20138, Italy

Location

Cardurion Investigative Site

Eindhoven, 5504 DL, Netherlands

Location

Cardurion Investigative Site

Groningen, 9713 AP, Netherlands

Location

Cardurion Investigative Site

Hardenberg, 7772 SE, Netherlands

Location

Cardurion Investigative Site

Sneek, 8601 ZR, Netherlands

Location

Cardurion Investigative Site

Zutphen, 7207 AE, Netherlands

Location

Cardurion Investigative Site

Dunedin, New Zealand

Location

Cardurion Investigative Site

Grodzisk Mazowiecki, 05-825, Poland

Location

Cardurion Investigative Site

Lodz, 92-213, Poland

Location

Cardurion Investigative Site

Lublin, 20-011, Poland

Location

Cardurion Investigative Site

Sopot, 81-717, Poland

Location

Cardurion Investigative Site

Torun, 87-100, Poland

Location

Cardurion Investigative Site

Warsaw, Poland

Location

Cardurion Investigative Site

Wroclaw, 50-556, Poland

Location

Cardurion Investigative Site

Wroclaw, 50-981, Poland

Location

Cardurion Investigative Site

Córdoba, 14004, Spain

Location

Cardurion Investigative Site

Málaga, 29010, Spain

Location

Cardurion Investigative Site

Santiago de Compostela, 15706, Spain

Location

Cardurion Investigative Site

Seville, 41009, Spain

Location

Cardurion Investigative Site

Valencia, 46026, Spain

Location

Cardurion Investigative Site

Kaohsiung City, Taiwan

Location

Cardurion Investigative Site

Taipei, Taiwan

Location

Cardurion Investigative Site

Taipei County, Taiwan

Location

Cardurion Investigative Site

Taoyuan District, Taiwan

Location

Cardurion Investigative Site

Bridgend, CF31 1RQ, United Kingdom

Location

Cardurion Investigative Site

Chichester, PO19 6SE, United Kingdom

Location

Cardurion Investigative Site

Dundee, DD1 9SY, United Kingdom

Location

Cardurion Investigative Site

Glasgow, G81 4DY, United Kingdom

Location

Cardurion Investigative Site

Harrow, HA1 3UJ, United Kingdom

Location

Cardurion Investigative Site

Isleworth, TW7 6AF, United Kingdom

Location

Cardurion Investigative Site

London, SE5 9RS, United Kingdom

Location

Cardurion Investigative Site

London, W1T 7HA, United Kingdom

Location

Cardurion Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic; Cardiovascular Diseases; Heart Diseases

Study Officials

• Gail Berman

  Senior VP Head, Clinical Development Cardurion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: January 22, 2024
• Study Start: February 13, 2024
• Primary Completion: September 2, 2025
• Study Completion: September 2, 2025
• Last Updated: November 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); GB (9); NL (5); HU (5); US (22); BU (7); DE (5); AU (1); ES (5); TW (4); CA (6); PL (8); NZ (1); BE (2); CZ (3)