A Phase II Clinical Trial of HRS-1893 in the Treatment of Heart Failure With Preserved Ejection Fraction

Официальное название

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial on the Efficacy and Safety of HRS-1893 in the Treatment of Heart Failure With Preserved Ejection Fraction

Обзор

This study aims to evaluate the safety and tolerability of HRS-1893 in subjects with heart failure with preserved ejection fraction.

Вмешательства

• Препарат HRS-1893 Tablet
  HRS-1893 tablet.
• Препарат HRS-1893 Tablet Placebo
  HRS-1893 tablet placebo.

Первичные конечные точки

• Incidence and severity of adverse events (AEs). [Срок оценки: Week 24.]

Вторичные конечные точки (6)

• Change from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP). [Срок оценки: Week 12 and Week 24.]
• Change from baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). [Срок оценки: Week 12 and Week 24.]
• Proportion of heart failure patients with preserved ejection fraction with an improvement of ≥1 NYHA functional class from baseline. [Срок оценки: Week 12 and Week 24.]
• Change from baseline in total distance walked during the six-minute walk test (6MWT). [Срок оценки: Week 12 and Week 24.]
• Change from baseline in resting left ventricular ejection fraction (LVEF). [Срок оценки: Week 12 and Week 24.]
• Plasma concentration of HRS-1893. [Срок оценки: Up to about 29 weeks.]

Критерии участия

Критерии включения

• Age ≥ 40 years at screening, regardless of gender;
• Body mass index < 35 kg/m²;
• Diagnosed with chronic heart failure before screening, and meeting relevant diagnostic criteria during the screening period: (1) Transthoracic echocardiography (TTE) at screening showing a resting left ventricular ejection fraction (LVEF) ≥ 60%; (2) Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) during the screening period; (3) Echocardiography showing structural or functional abnormalities of the heart, etc.;
• New York Heart Association (NYHA) classification of II or III at screening;
• KCCQ-CSS score between ≥25 and ≤75 at screening;
• Resting oxygen saturation >90% without supplemental oxygen at screening;
• Female participants of childbearing potential must have a negative serum pregnancy test before the first dose and must not be breastfeeding during the study. Female participants of childbearing potential and male participants whose partners are women of childbearing potential must agree to avoid donating sperm/eggs from the time of signing the informed consent until three months after the last dose of the study drug and comply with relevant contraceptive requirements;
• Understand the study procedures and methods, voluntarily participate in this trial, and provide written informed consent.

Критерии исключения

• Previously diagnosed or found during screening with hypertrophic cardiomyopathy (HCM), or having infiltrative/genetic/storage diseases that cause heart failure with preserved ejection fraction (HFpEF)/myocardial hypertrophy (such as amyloidosis, Fabry disease, Noonan syndrome with left ventricular hypertrophy), or complete M protein or monoclonal light chain (such as κ or λ) detected in serum protein electrophoresis and serum immunofixation electrophoresis during screening (researchers may deem not applicable if amyloidosis/multiple myeloma are excluded);
• Previously diagnosed or found during screening with hyperthyroidism;
• At any time in their clinical history, previously experienced left ventricular systolic dysfunction (LVEF <45%);
• History of syncope or sustained ventricular tachycardia within 6 months prior to screening;
• Previously experienced cardiac arrest with resuscitation at any time or received ICD therapy for life-threatening ventricular arrhythmia within 6 months prior to screening;
• Previously diagnosed or found during screening with atrial fibrillation;
• Coronary artery disease (stenosis >70% in one or more coronary arteries) or myocardial infarction: newly developed within 6 months prior to screening, or occurred more than 6 months prior without completed revascularization (such as percutaneous coronary intervention or coronary artery bypass grafting);
• Moderate to severe aortic stenosis, hemodynamically significant mitral stenosis, or severe mitral/tricuspid regurgitation at screening (as determined by the investigator);
• Severe chronic obstructive pulmonary disease (COPD) or other pulmonary diseases requiring home oxygen therapy, chronic nebulization/oral steroid treatment, or hospitalization due to pulmonary decompensation in the past 12 months;
• Acute respiratory infection at screening;
• Required intravenous diuretics, inotropes, vasodilators, or left ventricular assist device therapy for acute decompensated heart failure within 30 days prior to screening;
• Clinically significant history of malignancy within the past 5 years (excluding cancers that have been confirmed cured or in remission for ≥5 years, basal or squamous cell skin cancer that was radically excised within 5 years, carcinoma in situ of the cervix, and excised colon polyps);
• Electrocardiogram abnormalities posing safety risks at screening (as determined by the investigator, such as second-degree type II AV block, complete AV block, symptomatic ventricular arrhythmias, torsades de pointes, etc.);
• Any clinically significant abnormal screening laboratory values during screening deemed unsuitable for enrollment by the investigator;
• Positive result in any infectious disease screening during screening, including hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, HIV antibody (or AIDS virus antibody or P24 antigen);
• Inability to complete the six-minute walk test during screening (e.g., due to leg fractures, post-stroke mobility impairment);
• Patients who received β-blockers, diltiazem, or verapamil prior to screening but were not on a stable dose for more than 4 weeks before randomization, or are expected not to maintain the same medication regimen during the trial;
• Subjects who received heart failure medication treatment (diuretics, sodium-glucose co-transporter 2 inhibitors \[SGLT2i\], angiotensin receptor-neprilysin inhibitors \[ARNI\], mineralocorticoid receptor antagonists \[MRA\], angiotensin-converting enzyme inhibitors \[ACEI\], angiotensin II receptor blockers \[ARB\], glucagon-like peptide-1 \[GLP-1\] or GLP-1/glucose-dependent insulinotropic polypeptide \[GIP\]) prior to screening but have not been on a stable dose for more than 4 weeks before randomization, or are expected to be unable to maintain the same medication regimen during the trial;
• Subjects who used a myosin inhibitor within a period shorter than 5 half-lives before the trial drug administration;
• Subjects who participated in any drug or medical device clinical trial within 3 months prior to screening (participation in a clinical trial is defined as the subject having received the trial drug or medical device treatment);
• Other conditions deemed by the investigator that make the subject unsuitable for participation in the trial, such as conditions that may increase trial risk, affect the subject's protocol compliance, or impact the subject's ability to complete the trial due to physiological or psychological diseases or conditions.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Hospital Affiliated to Fudan University — Шанхай

Идентификаторы

NCT: NCT07269717 · HRS-1893-203

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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