A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)

NCT06215911 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CRD-750-2012023-508736-62
• Study Type: interventional
• Target: 557
• Locations: 19 countries
• Sites: 139

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 reduced ejection fraction.

Conditions

Heart Failure; Heart Failure With Reduced Ejection Fraction; Cardiovascular Diseases; Heart Diseases

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

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

  Baseline to Week 12

Secondary Outcomes (10)

• Change in biomarkers at Week 12 - NT-proBNP

  Baseline to Week 12

• 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

Study Arms (4)

Tovinontrine (CRD-750) - low dose

EXPERIMENTAL

Drug: Tovinontrine (CRD-750)

Tovinontrine (CRD-750) - medium dose

EXPERIMENTAL

Drug: Tovinontrine (CRD-750)

Tovinontrine (CRD-750) - high dose

EXPERIMENTAL

Drug: Tovinontrine (CRD-750)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tovinontrine (CRD-750) DRUG

Tablets administered orally

Tovinontrine (CRD-750) - high dose; Tovinontrine (CRD-750) - low dose; Tovinontrine (CRD-750) - medium dose

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% by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening;
• Has NT-proBNP level ≥ 600 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 ≥ 1000 pg/mL at the time of Screening;
• Is on stable optimized doses of guideline-directed HF therapy, per Investigator's clinical judgement, for a minimum of 4 weeks prior to the time of Screening and during Screening, 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 a documented EF \>40% 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 (139)

Cardurion Investigative Site

Birmingham, Alabama, 35233, United States

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Cardurion Investigative Site

Little Rock, Arkansas, 72204, United States

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Cardurion Investigative Site

Beverly Hills, California, 90211, United States

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Cardurion Investigative Site

Orange, California, 92868, United States

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Cardurion Investigative Site

Torrance, California, 90502, United States

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Cardurion Investigative Site

Van Nuys, California, 91405, United States

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Cardurion Investigative Site

Jacksonville, Florida, 32216, United States

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Cardurion Investigative Site

Miami, Florida, 33137, United States

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Cardurion Investigative Site

Hazel Crest, Illinois, 60429, United States

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Cardurion Investigative Site

Peoria, Illinois, 61636, United States

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Cardurion Investigative Site

Alexandria, Louisiana, 71301, United States

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Cardurion Investigative Site

Covington, Louisiana, 70433, United States

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Cardurion Investigative Site

Baltimore, Maryland, 21201, United States

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Cardurion Investigative Site

St Louis, Missouri, 63110, United States

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Cardurion Investigative Site

Omaha, Nebraska, 68198, United States

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Cardurion Investigative Site

Buffalo, New York, 14215, United States

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Cardurion Investigative Site

New York, New York, 10025, United States

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Cardurion Investigative Site

Cleveland, Ohio, 44195, United States

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Cardurion Investigative Site

Oklahoma City, Oklahoma, 73135, United States

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Cardurion Investigative Site

Rapid City, South Dakota, 57701, United States

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Cardurion Investigative Site

Nashville, Tennessee, 37232, United States

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Cardurion Investigative Site

Dallas, Texas, 75226, United States

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Cardurion Investigative Site

McKinney, Texas, 75069, United States

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Cardurion Investigative Site

Burlington, Vermont, 05401, United States

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Cardurion Investigative Site

Seattle, Washington, 98195, United States

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Cardurion Investigative Site

Madison, Wisconsin, 53792, United States

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Cardurion Investigative Site

Southport, Queensland, 4222, Australia

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Cardurion Investigative Site

Chermside, 4032, Australia

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Cardurion Investigative Site

Perth, Australia

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Cardurion Investigational Site

Bruges, 8000, Belgium

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Cardurion Investigative Site

Brussels, 1070, Belgium

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Cardurion Investigative Site

Brussels, Belgium

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Cardurion Investigative Site

Genk, Belgium

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Cardurion Investigative Site

Ghent, 9000, Belgium

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Cardurion Investigative Site

Hasselt, 3500, Belgium

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Cardurion Investigative Site

Kortrijk, 8500, Belgium

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Cardurion Investigative Site

Sint-Niklaas, 9100, Belgium

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Cardurion Investigative Site

Burgas, 8008, Bulgaria

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Cardurion Investigative Site

Gabrovo, 5300, Bulgaria

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Cardurion Investigative Site

Pazardzhik, 4400, Bulgaria

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Cardurion Investigative Site

Plovdiv, 4002, Bulgaria

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Cardurion Investigative Site

Plovdiv, 4003, Bulgaria

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Cardurion Investigative Site

Rousse, 7000, Bulgaria

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Cardurion Investigative Site

Sofia, 1000, Bulgaria

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Cardurion Investigative Site 2

Sofia, 1233, Bulgaria

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Cardurion Investigative Site

Sofia, 1233, Bulgaria

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Cardurion Investigative Site

Stara Zagora, 6000, Bulgaria

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Cardurion Investigative Site

Veliko Tarnovo, 5006, Bulgaria

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Cardurion Investigative Site

Cambridge, Ontario, N1R 6V6, Canada

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Cardurion Investigative Site

Hamilton, Ontario, L8L 2X2, Canada

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Cardurion Investigative Site

Chicoutimi, Quebec, G7H 7K9, Canada

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Cardurion Investigative Site

Montreal, Quebec, Canada

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Cardurion Investigative Site

Sherbrooke, J1G 2E8, Canada

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Cardurion Investigative Site

Trois-Rivières, G9B 2N3, Canada

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Cardurion Investigative Site

Hradec Králové, 500 02, Czechia

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Cardurion Investigative Site

Hradec Králové, 500 05, Czechia

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Cardurion Investigative Site

Prague, 128 08, Czechia

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Cardurion Investigative Site

Tbilisi, 0102, Georgia

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Cardurion Investigative Site

Tbilisi, 0131, Georgia

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Cardurion Investigative Site

Tbilisi, 0141, Georgia

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Cardurion Investigative Site 2

Tbilisi, 0159, Georgia

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Cardurion Investigative Site

Tbilisi, 0159, Georgia

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Cardurion Investigative Site

Tbilisi, 0160, Georgia

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Cardurion Investigative Site

Tbilisi, 0186, Georgia

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Cardurion Investigative Site

Berlin, Brandenburg, 10787, Germany

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Cardurion Investigative Site

Elsterwerda, Brandenburg, 04910, Germany

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Cardurion Investigative Site

Papenburg, Lower Saxony, 26871, Germany

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Cardurion Investigative Site

Dresden, 01067, Germany

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Cardurion Investigative Site

Magdeburg, 39120, Germany

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Cardurion Investigative Site

Balatonfüred, 8230, Hungary

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Cardurion Investigative Site

Budapest, 1148, Hungary

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Cardurion Investigative Site

Budapest, H-1122, Hungary

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Cardurion Investigative Site

Gyöngyös, 3200, Hungary

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Cardurion Investigative Site

Hatvan, 3000, Hungary

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Cardurion Investigative Site

Kaposvár, 7400, Hungary

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Cardurion Investigative Site

Orosháza, 5900, Hungary

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Cardurion Investigative Site

Zalaegerszeg, 8900, Hungary

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Cardurion Investigative Site

Bergamo, Italy

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Cardurion Investigative Site

Milan, 20138, Italy

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Cardurion Investigative Site

Napoli, Italy

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Cardurion Investigative Site

Rozzano, Italy

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Cardurion Investigative Site

Riga, Latvia

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Cardurion Investigative Site

Kaunas, Lithuania

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Cardurion Investigative Site

Klaipėda, Lithuania

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Cardurion Investigative Site

Panevezys, Lithuania

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Cardurion Investigative Site

Goes, 4462 RA, Netherlands

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Cardurion Investigative Site

Groningen, 9713 GZ, Netherlands

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Cardurion Investigative Site

Hardenberg, 7772 SE, Netherlands

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Cardurion Investigative Site

Sneek, 8601 ZR, Netherlands

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Cardurion Investigative Site

The Hague, 2545 AA, Netherlands

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Cardurion Investigative Site

Utrecht, 3582 KE, Netherlands

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Cardurion Investigative Site

Veldhoven, 5504 DB, Netherlands

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Cardurion Investigative Site

Zutphen, 7207 AE, Netherlands

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Cardurion Investigative Site

Christchurch, New Zealand

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Cardurion Investigative Site

Dunedin, New Zealand

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Cardurion Investigative Site

Grodzisk Mazowiecki, 05-825, Poland

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Cardurion Investigative Site

Krakow, 31-216, Poland

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Cardurion Investigative Site

Lodz, 92-213, Poland

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Cardurion Investigative Site

Lodz, 94-255, Poland

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Cardurion Investigative Site

Lodz, Poland

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Cardurion Investigative Site

Lublin, 20-011, Poland

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Cardurion Investigative Site

Lublin, 20-049, Poland

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Cardurion Investigative Site

Sopot, 81-717, Poland

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Cardurion Investigative Site

Szczecin, Poland

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Cardurion Investigative Site

Torun, 87-100, Poland

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Cardurion Investigative Site

Warsaw, 04-628, Poland

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Cardurion Investigative Site

Wroclaw, 50-556, Poland

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Cardurion Investigative Site

Wroclaw, 50-981, Poland

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Cardurion Investigative Site

Bardejov, Slovakia

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Cardurion Investigative Site

Bratislava, Slovakia

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Cardurion Investigative Site

Handlová, 972 51, Slovakia

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Cardurion Investigative Site

Košice, 040 022, Slovakia

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Cardurion Investigative Site

Košice, Slovakia

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Cardurion Investigative Site

Nitra, 949 01, Slovakia

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Cardurion Investigative Site

Prešov, 080 01, Slovakia

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Cardurion Investigative Site

Žilina, Slovakia

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Cardurion Investigative Site

El Palmar, Murcia, 30120, Spain

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Cardurion Investigative Site

Alicante, 03010, Spain

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Cardurion Investigative Site

Córdoba, 14004, Spain

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Cardurion Investigative Site

Madrid, 28041, Spain

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Cardurion Investigative Site

Málaga, 29010, Spain

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Cardurion Investigative Site

Santiago de Compostela, 15706, Spain

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Cardurion Investigative Site

Seville, 41009, Spain

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Cardurion Investigative Site

Valencia, 46026, Spain

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Cardurion Investigative Site

Kaohsiung City, 80756, Taiwan

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Cardurion Investigative Site

New Taipei City, 243, Taiwan

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Cardurion Investigative Site

Taichung, 407219, Taiwan

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Cardurion Investigative Site

Taipei, 100225, Taiwan

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Cardurion Investigative Site

Taipei, 10507, Taiwan

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Cardurion Investigative Site

Wythenshawe, Manchester, M23 9QZ, United Kingdom

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Cardurion Investigative Site

Bridgend, CF31 1RQ, United Kingdom

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Cardurion Investigative Site

Chichester, PO19 6SE, United Kingdom

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Cardurion Investigative Site

Dundee, DD1 9SY, United Kingdom

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Cardurion Investigative Site

Glasgow, G81 4DY, United Kingdom

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Cardurion Investigative Site

Harrow, HA1 3UJ, United Kingdom

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Cardurion Investigative Site

Isleworth, TW7 6AF, United Kingdom

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Cardurion Investigative Site

London, NW1 2BU, United Kingdom

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Cardurion Investigative Site

London, SE5 9RS, United Kingdom

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Cardurion Investigative Site

Southampton, SO16 6YD, United Kingdom

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MeSH Terms

Conditions

Heart Failure; 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: October 10, 2025
• Study Completion: October 10, 2025
• Last Updated: November 17, 2025

Record last verified: 2025-08

Locations

GE (7); BU (11); HU (8); CA (6); CZ (3); DE (5); IT (4); AU (3); LA (1); NL (8); ES (8); LI (3); BE (8); SL (8); US (26); GB (10); TW (5); PL (13); NZ (2)