NCT06215911已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 557
- 试验地点
- 142
- 主要终点
- Change in biomarkers from Baseline to Week 12 - NT-proBNP by treatment group
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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.
研究组 & 干预措施
Tovinontrine (CRD-750) - high dose
Experimental
干预措施: Tovinontrine (CRD-750) (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
Tovinontrine (CRD-750) - medium dose
Experimental
干预措施: Tovinontrine (CRD-750) (Drug)
Tovinontrine (CRD-750) - low dose
Experimental
干预措施: Tovinontrine (CRD-750) (Drug)
结局指标
主要结局
Change in biomarkers from Baseline to Week 12 - NT-proBNP by treatment group
时间窗: Baseline to Week 12
The percent change in plasma NT-proBNP from Baseline to Week 12.
次要结局
- Change in the biomarker ratio at Week 12 - BNP(Baseline to Week 12)
- Treatment Emergent Adverse Events (TEAEs)(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 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)
- The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-Clinical Summary Score(Baseline to Week 12)
- The change from baseline in the Kansas City Cardiomyopathy Questionnaire 23- Overall Summary Score(Baseline to Week 12)
- The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-CSS - Categorical(Week 12)
- New York Heart Association Classification(Week 12)
- Treatment Emergent Adverse Events (TEAEs)(Baseline to Week 12)
研究者
研究点 (142)
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相关资讯
Cardurion to Present Phase 2 Results for PDE9 Inhibitor Tovinontrine in Both Major Types of Heart Failure- Cardurion Pharmaceuticals will present Phase 2 CYCLE trial results for tovinontrine (CRD-750), a novel PDE9 inhibitor, at the HFSA Annual Scientific Meeting in Phoenix, Arizona, October 9–12, 2026.
- Tovinontrine is an orally administered PDE9 inhibitor that enhances the natriuretic peptide signaling pathway, and Cardurion is the first company to bring a PDE9 inhibitor into clinical development for chronic heart failure.
- The global, multi-center Phase 2 trials (NCT06215911 and NCT06215586) assess safety and efficacy in both heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).
- Despite current standard of care, a large unmet need remains, as approximately 6.7 million U.S. adults have heart failure and about 50 percent die within five years of diagnosis.22 days agoCardurion Completes Enrollment in Phase 2 Trials for Novel Heart Failure Drug CRD-750- Cardurion Pharmaceuticals has completed enrollment in two Phase 2 trials evaluating CRD-750, the first clinical-stage PDE9 inhibitor for chronic heart failure treatment.
- The CYCLE trials enrolled approximately 860 patients across both heart failure subtypes, with CYCLE-1-REF testing three doses in 560 HFrEF patients and CYCLE-2-PEF evaluating one dose in 300 HFpEF patients.
- CRD-750 targets phosphodiesterase 9 inhibition to enhance natriuretic peptide signaling, addressing a significant unmet medical need in heart failure where 50% of patients die within five years of diagnosis.
- The trials use NT-proBNP reduction as the primary endpoint, a validated biomarker previously used in approved heart failure therapies, with results expected to be presented at future medical meetings.last year