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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06215911




Registration number
NCT06215911
Ethics application status
Date submitted
13/12/2023
Date registered
22/01/2024
Date last updated
16/04/2025

Titles & IDs
Public title
A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)
Scientific 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
Secondary ID [1] 0 0
2023-508736-62
Secondary ID [2] 0 0
CRD-750-201
Universal Trial Number (UTN)
Trial acronym
Cycle-1-REF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Heart Failure With Reduced Ejection Fraction 0 0
Cardiovascular Diseases 0 0
Heart Diseases 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tovinontrine (CRD-750)
Treatment: Drugs - Placebo

Experimental: Tovinontrine (CRD-750) - low dose -

Experimental: Tovinontrine (CRD-750) - medium dose -

Experimental: Tovinontrine (CRD-750) - high dose -

Placebo comparator: Placebo -


Treatment: Drugs: Tovinontrine (CRD-750)
Tablets administered orally

Treatment: Drugs: Placebo
Tablets administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in biomarkers from Baseline to Week 12 - NT-proBNP
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [1] 0 0
Change in biomarkers at Week 12 by treatment group - NT-proBNP
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [2] 0 0
Change in biomarkers at week 12 by treatment group - cGMP
Timepoint [2] 0 0
Baseline to Week 12
Secondary outcome [3] 0 0
Change in biomarkers at week 12 by treatment group - BNP
Timepoint [3] 0 0
Baseline to Week 12
Secondary outcome [4] 0 0
Change in the biomarker ratio at Week 12 - NT-proBNP
Timepoint [4] 0 0
Baseline to Week 12
Secondary outcome [5] 0 0
Change in the biomarker ratio at Week 12 - BNP
Timepoint [5] 0 0
Baseline to Week 12
Secondary outcome [6] 0 0
Kansas City Cardiomyopathy Questionnaire-23-Clinical Summary Score
Timepoint [6] 0 0
Baseline to Week 12
Secondary outcome [7] 0 0
Kansas City Cardiomyopathy Questionnaire 23- Overall Summary Score
Timepoint [7] 0 0
Baseline to Week 12
Secondary outcome [8] 0 0
New York Heart Association Classification
Timepoint [8] 0 0
Baseline to Week 12
Secondary outcome [9] 0 0
Treatment Emergent Adverse Events (TEAEs)
Timepoint [9] 0 0
Baseline to Week 12
Secondary outcome [10] 0 0
Changes in laboratory assessments
Timepoint [10] 0 0
Baseline to Week 12
Secondary outcome [11] 0 0
Changes in vital sign measurement: systolic and diastolic blood pressure
Timepoint [11] 0 0
Baseline to Week 12
Secondary outcome [12] 0 0
Changes in vital sign measurement: pulse rate
Timepoint [12] 0 0
Baseline to Week 12
Secondary outcome [13] 0 0
Changes in vital sign measurement: respiratory rate
Timepoint [13] 0 0
Baseline to Week 12
Secondary outcome [14] 0 0
Changes in vital sign measurement: body temperature
Timepoint [14] 0 0
Baseline to Week 12
Secondary outcome [15] 0 0
Changes in physical examination
Timepoint [15] 0 0
Baseline to Week 12
Secondary outcome [16] 0 0
Changes in 12-lead electrocardiogram (ECG) measurements
Timepoint [16] 0 0
Baseline to Week 12
Secondary outcome [17] 0 0
Assessment of pharmacokinetics (PK): PK effect on NT-proBNP
Timepoint [17] 0 0
Baseline to Week 12
Secondary outcome [18] 0 0
Assessment of pharmacokinetics (PK): PK effect on plasma cGMP
Timepoint [18] 0 0
Baseline to Week 12

Eligibility
Key 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;
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Cardurion Investigative Site - Southport
Recruitment hospital [2] 0 0
Cardurion Investigative Site - Chermside
Recruitment postcode(s) [1] 0 0
4222 - Southport
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
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Nebraska
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United States of America
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New York
Country [11] 0 0
United States of America
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Ohio
Country [12] 0 0
United States of America
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Oklahoma
Country [13] 0 0
United States of America
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South Dakota
Country [14] 0 0
United States of America
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Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Vermont
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Belgium
State/province [19] 0 0
Brugge
Country [20] 0 0
Belgium
State/province [20] 0 0
Bruxelles
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Belgium
State/province [22] 0 0
Kortrijk
Country [23] 0 0
Belgium
State/province [23] 0 0
Sint-Niklaas
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Burgas
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Gabrovo
Country [26] 0 0
Bulgaria
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Pazardzhik
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Bulgaria
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Plovdiv
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Bulgaria
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Ruse
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Bulgaria
State/province [29] 0 0
Sofia
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Bulgaria
State/province [30] 0 0
Stara Zagora
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Veliko Tarnovo
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
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Canada
State/province [33] 0 0
Quebec
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Canada
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Sherbrooke
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Canada
State/province [35] 0 0
Trois-Rivières
Country [36] 0 0
Czechia
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Hradec Kralove
Country [37] 0 0
Czechia
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Hradec Králové
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Czechia
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Praha
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Georgia
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Tbilisi
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Germany
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Brandenburg
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Germany
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Lower Saxony
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Germany
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Dresden
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Germany
State/province [43] 0 0
Magdeburg
Country [44] 0 0
Hungary
State/province [44] 0 0
Balatonfured
Country [45] 0 0
Hungary
State/province [45] 0 0
Budapest
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Hungary
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Gyöngyös
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Hungary
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Hatvan
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Hungary
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Kaposvár
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Hungary
State/province [49] 0 0
Oroshaza
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Hungary
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Zalaegerszeg
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Italy
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Milano
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Netherlands
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Den Haag
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Goes
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Groningen
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Hardenberg
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Sneek
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Utrecht
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Veldhoven
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Netherlands
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Zutphen
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Poland
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Grodzisk Mazowiecki
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Kraków
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Lublin
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Sopot
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Torun
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Wroclaw
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Lódz
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Spain
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Murcia
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Alicante
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Spain
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Córdoba
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Santiago De Compostela
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Spain
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Sevilla
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Spain
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Valencia
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Taiwan
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Kaohsiung City
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Taiwan
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New Taipei City
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Taiwan
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Taipei
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United Kingdom
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Manchester
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Bridgend
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Chichester
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Dundee
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Glasgow
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Harrow
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United Kingdom
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Isleworth
Country [85] 0 0
United Kingdom
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London
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cardurion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gail Berman
Address 0 0
Senior VP Head, Clinical Development Cardurion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gail Berman
Address 0 0
Country 0 0
Phone 0 0
617-863-8088
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06215911