NCT07675668尚未招募2 期
A Phase 2, Multi-Regional, Open-label, Three-Part Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Aom0304 in Adult Patients With Symptomatic Hypertrophic Cardiomyopathy
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 56
- 主要终点
- To evaluate the safety and tolerability of Aom0304 in participants with HCM
研究概览
简要总结
The goal of this clinical trial is designed to characterise the safety, tolerability, efficacy, and PK of Aom0304 across oHCM and nHCM populations and to inform dose selection for future Phase 3 development. The main questions it aims to answer are:
- Which dose is safe and tolerant of Aom0304 in participants with HCM?
- Which dose is effective of 12 weeks of Aom0304 treatment in participants with oHCM or nHCM? Researchers will compare different doses of Aom0304 to see which works best. All participants will receive Aom0304, but at different dose levels depending on which cohort they joined.
Participants will:
- Undergo screening up to 28 days before enrollment to confirm eligibility
- Adjust dose every 2 weeks assessed by the Investigator according to predefined criteria at Titration Phase (Week 1 Day 1 to Week 8).
- Continuation of the last tolerated and effective dose; no further escalation is permitted at Maintenance Phase (Week 8 to Week 12).
- Study drug discontinued and follow up at Off-treatment Follow-up Period (at the end of Week 12 to Week 16).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent according to federal, local, and institutional guidelines before the first study-specific procedure.
- •Men or women participants aged 18 to 70 years (both inclusive) at Screening.
- •Documented diagnosed with HCM based on European Society of Cardiology/American College of Cardiology Foundation criteria: hypertrophied and non-dilated left ventricle in absence of other systemic or cardiac causes, with left ventricular wall thickness ≥ 15 mm at diagnosis or ≥ 13 mm with a positive family history of HCM, or a known gene mutation related to HCM.
- •Participants who are already treated with β-blockers, verapamil, diltiazem, or ranolazine should have been on stable doses for at least 4 weeks prior to Day 1 and anticipate remaining on the same medication regimen during the study.
- •Body weight must be ≥ 45 kg and body mass index 18 to 35 kg/m2 (both inclusive) at Screening.
- •LVEF ≥ 60% at Screening.
- •Symptomatic HCM defined as NYHA functional Class II or III at Screening.
- •Part-specific requirements at Screening:
- •Part 1: Post-Valsalva LVOT-G ≥ 30 mmHg and < 50 mmHg.
- •Part 2: Resting LVOT-G ≥ 50 mmHg or resting ≥ 30 mmHg with post-Valsalva ≥ 50 mmHg.
- •Part 3: Resting/post-Valsalva or exercise LVOT-G < 30 mmHg with NT-proBNP > 300 pg/mL.
- •Have adequate acoustic windows for accurate TTEs.
- •Female participants must not be pregnant or lactating and if sexually active, must be using 1 of the following acceptable contraceptive methods from the Screening through 3 months after the last dose of the study drug. Hormonal contraceptives are not considered highly effective contraceptive methods for this study. Acceptable contraceptive methods are listed as below.
- •Double-barrier method (eg, vasectomy or male using a condom and female using a diaphragm or cervical cap).
- •Barrier (eg, male using a condom) plus non-hormonal intrauterine device or intrauterine system.
- •Females are surgically sterile for 6 months or postmenopausal for 2 years. Permanent sterilisation includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal occlusion at least 6 months prior to Screening.
- •Females are considered postmenopausal if they have had amenorrhea for at least 2 years or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels are ≥ 40 IU/L at Screening (confirmed by at least 2 separate occasions during Screening Period).
- •Male participants with female partners (including postmenopausal partners) must agree to use highly effective contraceptive measures. from the Screening through 3 months after the last dose of study drug. Highly effective contraception is presented in Inclusion criterion #
- •As there may be a risk of drug being secreted in the ejaculate, male participants (including men who have had vasectomies) whose partners are currently pregnant, or not pregnant or capable of becoming pregnant, should use barrier methods for the duration of the study and 3 months following the last dose of study drug in order to prevent passing Aom0304 to the partner in the ejaculate.
- •Male and female participants must agree to not donate sperm or ova after the first dose of study drug until at least 3 months following last dose of study drug.
- •Must be able to complete the Dyspnoea Numeric Rating Scale (NRS) and the KCCQ per established guidelines.
- •Participants must be able to safely undergo CPET at Baseline and follow-up.
排除标准
- •Participants with clinically significant haematology or chemistry abnormalities at Screening, as determined by the Investigator, including but not limited to:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN).
- •Total bilirubin > 2 × ULN.
- •Haemoglobin < 9 g/dL.
- •Platelet count < 100000/µL.
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m².
- •Known hypersensitivity to Aom0304, or any of the components of the formulation of Aom0304, or alcohol.
- •History of sustained ventricular tachyarrhythmia or cardiac arrest.
- •Implanted cardioverter defibrillator (ICD) placement within 3 months prior to Screening or planned ICD placement during the study.
- •History of myocardial diseases other than HCM, including but not limited to: myocarditis, ischemic cardiomyopathy, dilated cardiomyopathy, cardiac amyloidosis, restrictive cardiomyopathy, Takotsubo syndrome, arrhythmogenic right ventricular cardiomyopathy.
- •Poor controlled hypertension, defined as systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg at Screening or Baseline despite stable antihypertensive therapy.
- •Participants who have been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or have plans for either treatment during the study period.
- •History of syncope with exercise within past 6 months prior to Screening.
- •Active infection, defined as any acute bacterial, viral, or fungal infection of any organ system (eg, respiratory, urinary, gastrointestinal, skin/soft tissue, cardiovascular, or central nervous system) requiring systemic antimicrobial therapy or considered to be clinically significant by the Investigator.
- •Current or recent (within 3 months prior to Screening) treatment with cardiac myosin inhibitors (eg, mavacamten, aficamten).
- •Persistent atrial fibrillation (AF), or paroxysmal AF with resting heart rate (HR) > 100 bpm within 1 year prior to Screening.
- •Have QT interval corrected by Fridericia's (QTcF) formula > 500 ms, or any other ECG abnormality considered by the Investigator to pose a risk to participant safety (eg, second degree atrioventricular block type II).
- •Aortic stenosis or fixed subaortic obstruction.
- •History of left ventricular systolic dysfunction (LVEF < 45%).
- •History of obstructive coronary artery disease (stenosis of > 70% of luminal diameter or > 50% of luminal diameter with ischemic symptoms in one or more coronary arteries), documented history of myocardial infarction or stroke.
- •History of malignancy of any type, with the following exceptions: in situ cervical cancer more than 5 years prior to Screening or surgically excised non-melanomatous skin cancers more than 2 years prior to Screening.
- •Positive serologic test at Screening for infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
- •Participants with positive alcohol or drug screen results considered clinically significant or indicative of ongoing abuse, as judged by the Investigator.
- •History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the Investigator, would pose a risk to participants' safety or interfere with the study evaluation, procedures, or completion.
- •Participated in a clinical trial where the participants received any investigational drug (or is currently using an investigational device) within 30 days prior to Screening, or at least 5 times the respective elimination half-life (whichever is longer).
- •Current use of tobacco- or nicotine-containing products > 20 cigarettes/day or equivalent.
- •Prior treatment with cardiotoxic agents such as doxorubicin or similar, or current treatment with antiarrhythmic drugs that have negative inotropic activity, eg, flecainide or propafenone.
- •Unable to comply with the study restrictions/requirements, including the number of required visits to the clinical site.
结局指标
主要结局
To evaluate the safety and tolerability of Aom0304 in participants with HCM
时间窗: Baseline to week 12
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), with LVEF \< 50% with abnormal vital signs, abnormal laboratory tests results, abnormal electrocardiograms (ECGs) and with changes in LVEF.
次要结局
- Change from Baseline in Left Ventricular Outflow Tract Gradient (LVOT-G) at Rest and Post-Valsalva in Participants with oHCM(Baseline to week 12)
- Change from Baseline in Peak Oxygen Consumption (pVO2)(Baseline to week 12)
- Change from Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)(Baseline to week 12)
- To assess the effects of 12 weeks of Aom0304 treatment on N-terminal pro B type natriuretic peptide (NT-proBNP)(Baseline to week 12)
- Proportion of participants achieving a LVOT-G response of resting LVOT-G < 30 mm Hg and post-Valsalva LVOT-Gs < 50 mm Hg(Baseline to week 12.)
- Proportion of Participants Achieving Post-Valsalva LVOT-G < 30 mmHg at Week 12(Baseline to week 12.)
- Proportion of Participants Achieving ≥ 20 mmHg Reduction in Post-Valsalva LVOT-G at Week 12(Baseline to week 12.)
研究者
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