A Study of IBI362 in Subjects With HFpEF or HFmrEF Combined With Obesity

Официальное название

A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of IBI362 in Subjects With HFpEF（Heart Failure With Preserved ejectIon Fraction）or HFmrEF（Heart Failure With Mildly Reduced Ejection Fraction）Combined With Obesity

Обзор

This is a multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of IBI362 in Chinese subjects with heart failure with ejection fraction retention/mild ejection fraction reduction (HFpEF/HFmrEF) combined with obesity (BMI≥28kg/㎡). This study will enroll about 141 NYHA Class II-III HFpEF/HFmrEF subjects combined with obesity. Eligible participants will be randomly assigned to IBI362 4 mg, IBI362 6 mg, or placebo at a ratio of 1:1:1, randomized by concomitant atrial fibrillation during screening (history/screening ECG). The trial period includes a 2-week screening period, a 52-week double-blind treatment period, and a 4-week safety follow-up period.

Вмешательства

• Другое placebo
  placebo administered subcutaneously(SC), once a week
• Препарат IBI362
  IBI362 administered subcutaneously(SC), once a week

Первичные конечные точки

• Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) [Срок оценки: From baseline (week 0) to week 36]
• Body weight change from baseline at week 36 [Срок оценки: From baseline (week 0) to week 36]

Вторичные конечные точки (12)

• Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Body weight change from baseline at week 52 [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Incidence, severity, and association with study drugs of adverse events [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Change in Systolic Blood Pressure (SBP) [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Change in Diastolic Blood Pressure(DBP) [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Change in ECG heart rate [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Change in N terminal pro B type natriuretic peptide（NT-proBNP） [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Change in hypersensitive C-reactive protein（hsCRP） [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Occurrence of serum anti-iBI362 antibody (ADA) before and after administration [Срок оценки: From baseliFrom baseline (week 0) to end of treatment (week 52)ne (week 0) to week 52]
• Occurrence of neutralizing antibody (NAb) before and after administration [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• Pharmacokinetics (PK): Maximum Concentration (Cmax) of IBI362 [Срок оценки: From baseline (week 0) to end of treatment (week 52)]
• PK: Area Under the Concentration Versus Time Curve (AUC) of IBI362 [Срок оценки: From baseline (week 0) to end of treatment (week 52)]

Критерии участия

Критерии включения

• Age ≥18 at the time of signing the informed consent.
• BMI≥28kg/m2.
• NYHA class II-III.
• There were no hospitalizations due to heart failure at screening visit (V1) to randomized visit (V2).
• KCCQ-CSS score < 80 during the screening period and before randomization.
• Medication for chronic diseases: If used before screening, the dose should be stable for ≥4 weeks; If not used before screening, the drug should also be stopped for ≥4 weeks.
• The women of childbearing potential（WOCBP） agrees to use the contraceptive method prescribed in this protocol for the entire study period and for 3 months after the final treatment. Pregnancy test results for fertile women during the screening period must be negative. Female subjects should not breastfeed.
• Voluntarily sign the informed consent form, and be willing to strictly abide by the requirements and restrictions of the informed consent form and the protocol throughout the study period, including but not limited to: maintaining a stable diet and exercise lifestyle, injecting the study drugs as planned, and keeping a study diary.

Критерии исключения

• myocardial infarction, stroke, or transient ischemic attacks, hospitalization for acute heart failure requiring any ventilatory and circulatory support devices (such as IABP ,I MPELLA, ECMO, CRRT, etc.) within 3 months before screening.
• Unstable angina pectoris or HF decompensation requiring IV diuretics, IV inotropes, or IV vasodilators within 30 days before screening.
• Poorly controlled hypertension at the screening stage, with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg. Or systolic blood pressure < 90mmHg during screening.
• Had previously undergone or planned to undergo bariatric surgery during the study period.
• The presence of endocrine diseases or medical history that may significantly affect body weight.
• Previous diagnosis of type 1 diabetes or specific type diabetes.
• Use of GLP-1R agonists or glucagon receptor (GLP-1R/GCGR) agonists or GIPR (Glucagon dependent insulinotropic polypeptide) within 3 months before screening receptor) /GLP-1R agonist or GIPR/GLP-1R/GCGR agonist; Participants who stopped using these drugs more than 3 months prior to screening due to lack of efficacy or intolerance should also be excluded.
• Use of insulin in the 3 months prior to screening to control diabetes, except for short-term (cumulative ≤14 days) use of insulin in acute conditions, such as acute illness, hospitalization, or elective surgery. The last insulin treatment was less than 14 days from the screening date.
• History of medullary thyroid carcinoma, multiple endocrine neoplasia (MEN) 2A or 2B or family history.
• Clinically significant gastric empting abnormalities (such as severe diabetic gastroparesis, gastric pyloric obstruction, etc.) or gastrointestinal surgery.
• Active or untreated malignancies were present within 5 years prior to screening, or clinical malignancies were in remission (except in subjects with no recurrence after surgery for basal cell and squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the prostate, or papillary thyroid carcinoma).
• A history of atopic reactions (clinical manifestations of severe or multiple allergies) or a history of clinically significant multiple or severe drug allergies, or intolerance to local glucocorticoids, Or severe post-treatment hypersensitivity reactions (including but not limited to erythema multiforme, linear immunoglobulin A dermatitis, toxic epidermal necrolysis, anaphylaxis, angioedema, or exfoliative dermatitis).
• History of organ transplantation (except corneal transplantation, autologous skin transplantation), or preparing to receive organ transplantation.
• The investigators identified major surgeries that might be planned during the study period that would affect the participants' ability to walk.
• Past suicidal thoughts or behaviors.
• The investigator believes that the subjects are not suitable to participate in the study because of any other factors (including previous serious mental illness) that may affect the efficacy, safety evaluation or compliance of the study.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fuwai Hospital, CAMS&PUMC — Пекин

Идентификаторы

NCT: NCT06862908 · CIBI362G201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗