2025-524469-25-00招募中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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AnaCardio AB
- 入组人数
- 167
- 试验地点
- 39
- 主要终点
- Absolute change from baseline in a composite echocardiography Z-score at Week 12; the composite Z-score integrates left ventricular stroke volume (LVSV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and left atrial minimal volume index (LAVImin).
研究概览
简要总结
To evaluate the effect of AC01 compared to placebo on cardiac structure and function assessed by echocardiography.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent, consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) good clinical practice (GCP) and local legislation, obtained before the initiation of any study-related procedures
- •Male study participants must agree to practice abstinence from heterosexual intercourse or use 2 effective means of contraception, 1 of which must be a barrier method, for the duration of the study and for at least 90 days after their last dose of study medication, if the partner is a woman of childbearing potential. If a female partner is of non-childbearing potential, the male study participant is excluded from contraceptive requirements.
- •Male or female, ≥18 to ≤85 years of age at signing of informed consent
- •History of CHF diagnosed ≥6 months before screening, and in New York Heart Association (NYHA) Class II to IV at screening
- •Chronic advanced HFrEF defined as: • LVEF ≤35% by local reading ≥ 6 months before screening (any imaging method) 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 >35% (or qualitatively described as less than moderately-severely reduced) between the 2 readings
- •Sinus rhythm or permanent, persistent, or paroxysmal AFF (AFF at screening is capped at maximum 15% of patients enrolled) with mean resting heart rate, measured as part of vital signs, of ≥55 and ≤90 bpm at screening, and ≥50 and ≤95 bpm at randomization (mean of the triplicate recording), regardless of rhythm.
- •NT-proBNP ≥ 400 pg/mL in sinus rhythm and ≥800 pg/mL in AFF at screening (confirmed by central laboratory).
- •Transvenous ICD for primary prevention in place and active, 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.
- •Female study participants of childbearing potential must use a highly effective method of contraception for at least 14 days before randomization, throughout the study, and for at least 90 days after their last dose of study treatment.
排除标准
- •Medical conditions: Known hypersensitivity or intolerance to AC01 or any other components of the AC01 or placebo formulations, including excipients.
- •History of any solid organ transplantation or anticipated to receive a transplantation during the study period.
- •Any existing surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of AC
- •Any of the following ECG findings at screening (local reading, mean of triplicate recording): QTcF >450 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 (i.e., >30 seconds), or Torsades—de Pointes (except if due to a reversible cause that no longer poses a threat), or congenital long QT syndrome. Family history of sudden cardiac death, unexplained death, long QT syndrome, or death from a primary dysrhythmia potentially associated with QT prolongation in any first degree relative i.e., parent, sibling or child.
- •Any cardiac rhythm, other than AFF, that could interfere with ECG or echocardiography interpretation, including but not limited to >20% of ventricular contractions on ECG strips being premature ventricular contractions including doublets, triplets, bigeminy, or trigeminy, or atrial or ventricular pacing.
- •Any ventricular tachycardia requiring anti-arrhythmic therapy, ICD shock, or anti-tachycardia pacing within 12 months before randomization.
- •Prior or concomitant therapy: 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.
- •Any acute or serious co-morbid condition (e.g., including but not limited to, projected life expectancy of less than 12 months due to non-cardiovascular causes, unplanned hospitalization within 28 days of randomization for reason other than HF, major infection or hematologic, hepatic (Child-Pugh class C), pancreatic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the judgment of the investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study
- •Treatment with systemic glucocorticoids for more than 7 days within 28 days of randomization or current treatment at randomization
- •Use of any drugs or substances known to be strong inducers of CYP3A4 enzyme (e.g., rifampin and phenytoin) within 28 days before randomization or planned to be used during the study period.
- •Use of any drugs or substances known to be strong inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir) within 7 days before randomization or planned to be used during the study period.
- •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.
- •Use of any drug that is known to prolong the QT interval as indicated by the Warnings and Precaution section of the product label (e.g., 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.
- •Prior and/or concomitant clinical study experience: Current or previous participation in any other interventional clinical study where the patient has received a dose of investigational medical product (IMP) within 4 weeks or 5 half-lives of the IMP, whichever is longest, before screening.
- •Diagnostic laboratory assessment (confirmed by central laboratory): Estimated glomerular filtration rate (eGFR) <20 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 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. An isolated increase in bilirubin in participants with known Gilbert’s syndrome is not a reason for exclusion.
- •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 (i.e. for >24 hours and ≤10 days) is capped at a maximum of 15% of patients enrolled.
- •Other: Intake of food or drinks known to interfere with CYP450 metabolic enzymes (e.g., grapefruit juice, cranberry juice, pomelo juice, star fruit, or Seville orange products) within 7 days before randomization and unwilling to avoid such food during the study period.
- •Women who are pregnant, breastfeeding, or who plan to become pregnant during the study period.
- •Participant or first-degree relative employed by or with ownership interest in the sponsor organization.
- •Factors expected to interfere with the patient’s availability or ability to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient’s and investigator’s knowledge (including ongoing substance abuse).
- •Active malignancy requiring chemotherapy, surgery, radiotherapy, or palliative care at screening.
- •Acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina), stroke or transient ischemic attack, severe ventricular arrhythmia (e.g., ventricular fibrillation or sustained ventricular tachycardia), or major cardiac intervention (e.g., implantation of cardiac closure devices, or catheter ablation), percutaneous coronary intervention, valvuloplasty/other cardiac valve repair or implantation, or cardiac surgery within 60 days before randomization; having any of these interventions planned during the study period; having any electrical or pharmacological cardioversion planned during the study period; or having any infusion therapy for HF planned during the study period.
- •Severe uncorrected valvular heart disease, hypertrophic or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease according to the investigator.
- •Systolic blood pressure >130 or ˂90 mmHg at screening, or >140 or ˂85 mmHg at randomization (mean of triplicate recording).
- •Uncontrolled diabetes mellitus, defined as HbA1c ≥9.0% (≥75 mmol/mol) at screening, or severe complications of diabetes such as pre-proliferative or proliferative diabetic retinopathy, macular edema, diabetic foot syndrome, or recent (within 12 months before randomization) primary diagnosis of severe hyperglycemia requiring hospitalization.
- •Body weight <50 kg or body mass index (BMI) <18 kg/m2 or >45 kg/m2 at screening.
研究组 & 干预措施
Placebo tablets have the same qualitative composition than Test IMP but contain no active drug substance.
Placebo
干预措施: Placebo tablets have the same qualitative composition than Test IMP but contain no active drug substance. (Drug)
AC01, AC01
Test
干预措施: AC01 (Drug)
结局指标
主要结局
Absolute change from baseline in a composite echocardiography Z-score at Week 12; the composite Z-score integrates left ventricular stroke volume (LVSV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and left atrial minimal volume index (LAVImin).
Absolute change from baseline in a composite echocardiography Z-score at Week 12; the composite Z-score integrates left ventricular stroke volume (LVSV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and left atrial minimal volume index (LAVImin).
次要结局
- Absolute change from baseline in LVSV at Week 12
- Absolute change from baseline in LVEF at Week 12
- Absolute change from baseline in LVESV at Week 12
- Absolute change from baseline in LAVImin at Week 12
研究者
Göran Westerberg
Scientific
AnaCardio AB
研究点 (39)
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