Clinical trial NCT06215911: A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Failure
Heart Failure With Reduced Ejection Fraction
Cardiovascular Diseases
Heart Diseases
Keywords: PDE9
PED9 Inhibitor
Heart Failure
CRD-750
Tovinontrine
HFrEF
Lead sponsor: Cardurion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-22
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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% 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;

Exclusion Criteria:

* 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;

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

Primary outcomes:
measure: Change in biomarkers from Baseline to Week 12 - NT-proBNP
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in biomarkers at Week 12 by treatment group - NT-proBNP
timeFrame: Baseline to Week 12
measure: Change in biomarkers at week 12 by treatment group - cGMP
timeFrame: Baseline to Week 12
measure: Change in biomarkers at week 12 by treatment group - BNP
timeFrame: Baseline to Week 12
measure: Change in the biomarker ratio at Week 12 - NT-proBNP
timeFrame: Baseline to Week 12
measure: Change in the biomarker ratio at Week 12 - BNP
timeFrame: Baseline to Week 12
measure: Kansas City Cardiomyopathy Questionnaire-23-Clinical Summary Score
timeFrame: Baseline to Week 12
measure: Kansas City Cardiomyopathy Questionnaire 23- Overall Summary Score
timeFrame: Baseline to Week 12
measure: New York Heart Association Classification
timeFrame: Baseline to Week 12
measure: Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline to Week 12
measure: Changes in laboratory assessments
timeFrame: Baseline to Week 12
measure: Changes in vital sign measurement: systolic and diastolic blood pressure
timeFrame: Baseline to Week 12
measure: Changes in vital sign measurement: pulse rate
timeFrame: Baseline to Week 12
measure: Changes in vital sign measurement: respiratory rate
timeFrame: Baseline to Week 12
measure: Changes in vital sign measurement: body temperature
timeFrame: Baseline to Week 12
measure: Changes in physical examination
timeFrame: Baseline to Week 12
measure: Changes in 12-lead electrocardiogram (ECG) measurements
timeFrame: Baseline to Week 12
measure: Assessment of pharmacokinetics (PK): PK effect on NT-proBNP
timeFrame: Baseline to Week 12
measure: Assessment of pharmacokinetics (PK): PK effect on plasma cGMP
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardurion Investigative Site
state: Alabama
city: Little Rock
country: United States
facility: Cardurion Investigative Site
state: Arkansas
city: Beverly Hills
country: United States
facility: Cardurion Investigative Site
state: California
city: Orange
country: United States
facility: Cardurion Investigative Site
state: California
city: Torrance
country: United States
facility: Cardurion Investigative Site
state: California
city: Van Nuys
country: United States
facility: Cardurion Investigative Site
state: California
city: Jacksonville
country: United States
facility: Cardurion Investigative Site
state: Florida
city: Miami
country: United States
facility: Cardurion Investigative Site
state: Florida
city: Hazel Crest
country: United States
facility: Cardurion Investigative Site
state: Illinois
city: Peoria
country: United States
facility: Cardurion Investigative Site
state: Illinois
city: Alexandria
country: United States
facility: Cardurion Investigative Site
state: Louisiana
city: Covington
country: United States
facility: Cardurion Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Cardurion Investigative Site
state: Maryland
city: Saint Louis
country: United States
facility: Cardurion Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Cardurion Investigative Site
state: Nebraska
city: Buffalo
country: United States
facility: Cardurion Investigative Site
state: New York
city: New York
country: United States
facility: Cardurion Investigative Site
state: New York
city: Cleveland
country: United States
facility: Cardurion Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Cardurion Investigative Site
state: Oklahoma
city: Rapid City
country: United States
facility: Cardurion Investigative Site
state: South Dakota
city: Nashville
country: United States
facility: Cardurion Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Cardurion Investigative Site
state: Texas
city: McKinney
country: United States
facility: Cardurion Investigative Site
state: Texas
city: Burlington
country: United States
facility: Cardurion Investigative Site
state: Vermont
city: Seattle
country: United States
facility: Cardurion Investigative Site
state: Washington
city: Madison
country: United States
facility: Cardurion Investigative Site
state: Wisconsin
city: Southport
country: Australia
facility: Cardurion Investigative Site
state: Queensland
city: Chermside
country: Australia
facility: Cardurion Investigative Site
city: Perth
country: Australia
facility: Cardurion Investigative Site
city: Brugge
country: Belgium
facility: Cardurion Investigational Site
city: Brussels
country: Belgium
facility: Cardurion Investigative Site
city: Bruxelles
country: Belgium
facility: Cardurion Investigative Site
city: Gent
country: Belgium
facility: Cardurion Investigative Site
city: Hasselt
country: Belgium
facility: Cardurion Investigative Site
city: Kortrijk
country: Belgium
facility: Cardurion Investigative Site
city: Sint-Niklaas
country: Belgium
facility: Cardurion Investigative Site
city: Burgas
country: Bulgaria
facility: Cardurion Investigative Site
city: Gabrovo
country: Bulgaria
facility: Cardurion Investigative Site
city: Pazardzhik
country: Bulgaria
facility: Cardurion Investigative Site
city: Plovdiv
country: Bulgaria
facility: Cardurion Investigative Site
city: Plovdiv
country: Bulgaria
facility: Cardurion Investigative Site
city: Ruse
country: Bulgaria
facility: Cardurion Investigative Site
city: Sofia
country: Bulgaria
facility: Cardurion Investigative Site
city: Sofia
country: Bulgaria
facility: Cardurion Investigative Site 2
city: Sofia
country: Bulgaria
facility: Cardurion Investigative Site
city: Stara Zagora
country: Bulgaria
facility: Cardurion Investigative Site
city: Veliko Tarnovo
country: Bulgaria
facility: Cardurion Investigative Site
city: Cambridge
country: Canada
facility: Cardurion Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Cardurion Investigative Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Cardurion Investigative Site
state: Quebec
city: Montréal
country: Canada
facility: Cardurion Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Cardurion Investigative Site
city: Trois-Rivières
country: Canada
facility: Cardurion Investigative Site
city: Hradec Kralove
country: Czechia
facility: Cardurion Investigative Site
city: Hradec Králové
country: Czechia
facility: Cardurion Investigative Site
city: Praha
country: Czechia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site 2
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Tbilisi
country: Georgia
facility: Cardurion Investigative Site
city: Berlin
country: Germany
facility: Cardurion Investigative Site
state: Brandenburg
city: Elsterwerda
country: Germany
facility: Cardurion Investigative Site
state: Brandenburg
city: Papenburg
country: Germany
facility: Cardurion Investigative Site
state: Lower Saxony
city: Dresden
country: Germany
facility: Cardurion Investigative Site
city: Magdeburg
country: Germany
facility: Cardurion Investigative Site
city: Balatonfured
country: Hungary
facility: Cardurion Investigative Site
city: Budapest
country: Hungary
facility: Cardurion Investigative Site
city: Budapest
country: Hungary
facility: Cardurion Investigative Site
city: Gyöngyös
country: Hungary
facility: Cardurion Investigative Site
city: Hatvan
country: Hungary
facility: Cardurion Investigative Site
city: Kaposvár
country: Hungary
facility: Cardurion Investigative Site
city: Oroshaza
country: Hungary
facility: Cardurion Investigative Site
city: Zalaegerszeg
country: Hungary
facility: Cardurion Investigative Site
city: Milano
country: Italy
facility: Cardurion Investigative Site
city: Klaipėda
country: Lithuania
facility: Cardurion Investigative Site
city: Panevėžys
country: Lithuania
facility: Cardurion Investigative Site
city: Den Haag
country: Netherlands
facility: Cardurion Investigative Site
city: Goes
country: Netherlands
facility: Cardurion Investigative Site
city: Groningen
country: Netherlands
facility: Cardurion Investigative Site
city: Hardenberg
country: Netherlands
facility: Cardurion Investigative Site
city: Sneek
country: Netherlands
facility: Cardurion Investigative Site
city: Utrecht
country: Netherlands
facility: Cardurion Investigative Site
city: Veldhoven
country: Netherlands
facility: Cardurion Investigative Site
city: Zutphen
country: Netherlands
facility: Cardurion Investigative Site
city: Grodzisk Mazowiecki
country: Poland
facility: Cardurion Investigative Site
city: Kraków
country: Poland
facility: Cardurion Investigative Site
city: Lublin
country: Poland
facility: Cardurion Investigative Site
city: Lublin
country: Poland
facility: Cardurion Investigative Site
city: Sopot
country: Poland
facility: Cardurion Investigative Site
city: Szczecin
country: Poland
facility: Cardurion Investigative Site
city: Torun
country: Poland
facility: Cardurion Investigative Site
city: Warszawa
country: Poland
facility: Cardurion Investigative Site
city: Wrocław
country: Poland
facility: Cardurion Investigative Site
city: Wrocław
country: Poland
facility: Cardurion Investigative Site
city: Łódź
country: Poland
facility: Cardurion Investigative Site
city: Łódź
country: Poland
facility: Cardurion Investigative Site
city: Bardejov
country: Slovakia
facility: Cardurion Investigative Site
city: Handlová
country: Slovakia
facility: Cardurion Investigative Site
city: Košice
country: Slovakia
facility: Cardurion Investigative Site
city: Nitra
country: Slovakia
facility: Cardurion Investigative Site
city: Prešov
country: Slovakia
facility: Cardurion Investigative Site
city: Žilina
country: Slovakia
facility: Cardurion Investigative Site
city: El Palmar
country: Spain
facility: Cardurion Investigative Site
state: Murcia
city: Alicante
country: Spain
facility: Cardurion Investigative Site
city: Córdoba
country: Spain
facility: Cardurion Investigative Site
city: Madrid
country: Spain
facility: Cardurion Investigative Site
city: Málaga
country: Spain
facility: Cardurion Investigative Site
city: Santiago De Compostela
country: Spain
facility: Cardurion Investigative Site
city: Sevilla
country: Spain
facility: Cardurion Investigative Site
city: Valencia
country: Spain
facility: Cardurion Investigative Site
city: Kaohsiung City
country: Taiwan
facility: Cardurion Investigative Site
city: New Taipei City
country: Taiwan
facility: Cardurion Investigative Site
city: Taichung
country: Taiwan
facility: Cardurion Investigative Site
city: Taipei
country: Taiwan
facility: Cardurion Investigative Site
city: Taipei
country: Taiwan
facility: Cardurion Investigative Site
city: Wythenshawe
country: United Kingdom
facility: Cardurion Investigative Site
state: Manchester
city: Bridgend
country: United Kingdom
facility: Cardurion Investigative Site
city: Chichester
country: United Kingdom
facility: Cardurion Investigative Site
city: Dundee
country: United Kingdom
facility: Cardurion Investigative Site
city: Glasgow
country: United Kingdom
facility: Cardurion Investigative Site
city: Harrow
country: United Kingdom
facility: Cardurion Investigative Site
city: Isleworth
country: United Kingdom
facility: Cardurion Investigative Site
city: London
country: United Kingdom
facility: Cardurion Investigative Site
city: London
country: United Kingdom
facility: Cardurion Investigative Site
city: Southampton
country: United Kingdom
facility: Cardurion Investigative Site
Study officials:
affiliation: Senior VP Head, Clinical Development Cardurion
name: Gail Berman
role: STUDY_DIRECTOR
References: