NCT07584967尚未招募2 期
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of 2 Dose Levels of the Oral Ghrelin Receptor Agonist AC01 Over 12 Weeks in Patients With Chronic Advanced Heart Failure With Reduced Ejection Fraction (HFrEF)
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- AnaCardio AB
- 入组人数
- 400
研究概览
简要总结
The primary purpose of the study is to evaluate the safety and efficacy of 2 doses of AC01 compared to placebo over 12 weeks in participants with chronic advanced HFrEF.
详细描述
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the safety and efficacy of the ghrelin-receptor agonist AC01 compared to placebo in participants with chronic advanced HFrEF. Approximately 400 participants will be randomized to 1 of 3 treatment arms: 3 milligram (mg) AC01, 1 milligram (mg) AC01, or placebo twice daily for 12 weeks. The primary objective is to evaluate the effect of AC01 compared to placebo on cardiac structure and function assessed by echocardiography.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of Chronic Heart Failure (CHF) diagnosed greater than or equal to (>=6) months before screening, and in NYHA Class II to IV at screening.
- •Chronic advanced HFrEF defined as:
- •LVEF less than or equal to (<=) 35 percentage (%) by local reading >=6 months before screening or a record of LVEF qualitatively described as severely reduced or moderately-severely reduced >=6 months before screening, and
- •LVEF <=35% at the screening echocardiography (confirmed by core lab), and
- •no known LVEF greater than (>) 35% (or qualitatively described as less than moderately-severely reduced) between the 2 readings.
- •Sinus rhythm or permanent, persistent, or paroxysmal atrial fibrillation flutter (AFF) (AFF at screening is capped at maximum 15% of participants enrolled) with mean resting heart rate of >=55 and <=90 beats per minute (bpm) at screening, and >=50 and <=95 bpm at randomization, regardless of rhythm.
- •NT-proBNP >=400 picograms per milliliter (pg/mL) in sinus rhythm and >=800 pg/mL in AFF at screening (confirmed by central laboratory).
- •Transvenous implantable cardioverter-defibrillator (ICD) for primary prevention with back-up pacing set at 40 bpm.
- •Treated with optimal, stable, medical therapy for HF consistent with prevailing local and international guidelines unless contraindicated or not tolerated, as judged and documented by the investigator.
排除标准
- •Any acute or serious co-morbid condition that could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.
- •Admitted to hospital with the primary reason of HF within 24 hours before randomization or currently hospitalized with the primary reason of HF for more than 10 days. Current hospitalization (>24 hours and <=10 days) is capped at a maximum of 15% of participants enrolled.
- •Acute coronary syndrome, stroke or transient ischemic attack, severe ventricular arrhythmia, or major cardiac intervention, percutaneous coronary intervention, valvuloplasty/other cardiac valve repair or implantation, or cardiac surgery within 60 days before randomization.
- •Systolic blood pressure >130 or ˂90 millimeters of mercury (mmHg) at screening, or >140 or ˂85 mmHg at randomization.
- •Uncontrolled diabetes mellitus, defined as Hemoglobin A1c (HbA1c) >=9.0% (>=75 millimoles per mole [mmol/mol]) at screening, or severe complications of diabetes.
- •Body weight <50 kilogram (kg) or body mass index (BMI) <18 kilograms per square meter (kg/m^2) or >45 kg/m^2 at screening.
- •Any of the following electrocardiogram (ECG) findings at screening: Corrected QT interval using Fridericia's formula (QTcF) >450 milliseconds (ms), 1st degree atrioventricular (AV) block with PQ >240 ms, or AV block 2nd or 3rd degree.
- •History of aborted cardiac arrest, sustained ventricular tachycardia, or Torsades-de Pointes, or congenital long QT syndrome. Family history of sudden cardiac death, unexplained death, long QT syndrome, or death from a primary dysrhythmia.
- •Cardiac resynchronization therapy, Cardiac Contractility Modulation, or pacemaker device other than the back-up pacing function of the ICD.
- •Mechanical hemodynamic support, kidney support, or ventilation within 7 days before randomization.
- •Treatment with i.v. inotropes, i.v. vasodilators, or i.v. vasopressors within 3 days before randomization.
- •Treatment with any i.v. diuretics or supplemental oxygen within 6 hours before randomization.
- •Use of any drugs or substances known to be strong inducers of Cytochrome P450 3A4 (CYP3A4) enzyme within 28 days before randomization or planned to be used during the study period or strong inhibitors of CYP3A4 within 7 days before randomization or planned to be used during the study period.
- •Use of any drug that is known to prolong the QT interval (for example, sotalol, dofetilide, macrolides, some antidepressants, and some antipsychotics) within 28 days before randomization or planned to be used during the study period.
- •Treatment changes in glucose lowering therapy within 28 days before randomization.
- •Estimated glomerular filtration rate (eGFR) <20 milliliters per minute per 1.73 square meters (mL/min/1.73 m2) according to the Chronic Kidney Disease Epidemiology Collaboration formula, planned renal replacement therapy within the next 6 months, or receiving dialysis at screening.
- •Serum potassium <3.5 or >5.2 milliequivalents per liter (mEq/L) at screening.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 *upper limit of normal (ULN) or total bilirubin >2 * ULN, or known cirrhosis, severe liver, or pancreatic disease at screening.
- •Use of any anti-arrhythmic drugs within 28 days before randomization or planned to be used during the study period, except for amiodarone, ivabradine, digoxin, and beta blockers.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will receive matching placebo orally BID for 12 weeks.
干预措施: Placebo (Other)
AC01 3 mg
Experimental
Participants will receive AC01 orally twice daily (BID) for 12 weeks.
干预措施: AC01 (Drug)
AC01 1 mg
Experimental
Participants will receive AC01 orally BID for 12 weeks.
干预措施: AC01 (Drug)
结局指标
主要结局
未指定
次要结局
- AUC,ss: Area Under the Concentration-Time Curve at Steady State of AC01 and its Metabolite M6(At Week 4 and Week 12)
- Cmax,ss: Maximum Observed Concentration at Steady State of AC01 and its Metabolite M6(At Week 4 and Week 12)
- Tmax,ss: Time to Reach Maximum Concentration at Steady State(At Week 4 and Week 12)
- Ctrough: Trough concentration at steady state of AC01 and its Metabolite M6(At Week 4 and Week 12)
- Rac (Cmax): Accumulation Ratio of Cmax for AC01 and its Metabolite M6(At Week 4 and Week 12)
- Rac (AUC): Accumulation Ratio of AUC for AC01 and its Metabolite M6(At Week 4 and Week 12)
研究者
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