NCT04836182已完成2 期
A Double-Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Study Assessing the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor of Angiotensinogen Production, Administered Subcutaneously Over 12 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 19
- 主要终点
- Percent Change in Plasma AGT Concentration From Baseline to Study Day 85
研究概览
简要总结
The purpose of this study is to evaluate the effect of IONIS-AGT-LRX weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) and to evaluate the effect of IONIS-AGT-LRx weekly SC injection on plasma AGT concentration and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels at each scheduled visit in chronic heart failure participants with reduced ejection fraction (HFrEF).
详细描述
This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 72 participants. Participants will be randomized in a 2:1 ratio to either IONIS-AGT-LRX or matching placebo and receive a once-weekly SC treatment. The length of participation in the study will be approximately 35 weeks, which includes an up to 10-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Females must be non-pregnant and non-lactating and of non- childbearing potential.
- •Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), she must be willing to use a highly effective contraceptive method
- •Screening NT-proBNP ≥ 600 picograms per milliliter (pg/mL) and less than (<) 8500 pg/mL
- •Established diagnosis of heart failure (HF) with reduced systolic function for at least 6 months prior to the screening visit (left ventricular ejection fraction, [LVEF] ≤ 40%
- •New York Heart Association class I-III
- •Participants should receive background standard of care for HFrEF. Therapy should have been individually optimized and stable for ≥ 4 weeks before randomization and include:
- •An angiotensin-converting-enzyme inhibitor (ACEi), or angiotensin II receptor blockers (ARBs) or sacubitril/valsartan (mandatory)
- •A beta-blocker (unless contraindicated or not tolerated)
- •A mineralocorticoid receptor antagonist (MRA, unless contraindicated or not tolerated)
排除标准
- •HF due to restrictive cardiomyopathy, active myocarditis, chemotherapy, hypertrophic cardiomyopathy, primary cardiac valve disease, non-compaction cardiomyopathy, or takotsubo cardiomyopathy.
- •Acute decompensated HF requiring intravenous (IV) diuretics, IV inotropes or IV vasodilators with discharge date within 30 days of screening or acute mechanical support (e.g., intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) with discharge date within 90 days of screening.
- •Symptomatic hypotension or systolic blood pressure (SBP) ≤ 90 millimeters of mercury (mmHg) at screening.
- •Uncontrolled hypertension (HTN) (SBP > 160 mmHg or diastolic blood pressure (BP) > 100 mmHg) prior to screening.
- •Heart transplant, and/or Left Ventricular Assist Device (LVAD) prior to screening or anticipated heart transplant or LVAD during the study.
- •Implantation of a cardiac resynchronization therapy device (CRT) within 3 months prior screening or intent to implant a CRT within 3 months after screening.
- •Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, carotid or other major surgery within 3 months of screening.
- •Coronary, valve or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after screening.
- •Severe pulmonary disease with any of the following:
- •Requirement of continuous (home) oxygen or
- •Known diagnosis of severe chronic obstructive pulmonary disease (as defined by the American Thoracic Society/European Respiratory Society) or severe restrictive lung disease, in the opinion of the investigator.
- •Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the opinion of the investigator.
- •Alanine aminotransferase/aspartate aminotransferase (ALT/AST) > 2.0 × upper limit of normal (ULN).
- •Total bilirubin ≥ 1.5 × ULN (participants with total bilirubin ≥ 1.5 × ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN, and known to have Gilbert's disease).
- •Platelets < 100,000/millimeter^3 (mm^3).
- •Urine protein creatinine ratio (UPCR) ≥ 500 milligrams per gram (mg/g).
- •Hemoglobin A1c (HbA1c) > 9.5% or uncontrolled diabetes per investigator judgement.
- •Estimated glomerular filtration rate (eGFR) < 30 milliliters/ minute /1.73 m^2 (mL/min/1.73 meter^2) at screening.
- •Abnormal thyroid function tests with clinical significance per investigator judgement.
- •Serum potassium > 5.1 millimoles per liter (mmol/L) at screening.
- •Requirement of treatment with both ACEi and ARBs.
- •Previous history of intolerance to ACEi or ARBs or history of hyperkalemia.
研究组 & 干预措施
IONIS-AGT-LRx
Experimental
IONIS-AGT-LRX by subcutaneous injection once-weekly
干预措施: IONIS-AGT-LRx (Drug)
Placebo
Placebo Comparator
Matching placebo by subcutaneous injection once-weekly
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change in Plasma AGT Concentration From Baseline to Study Day 85
时间窗: Baseline to Day 85
次要结局
- Change in Plasma AGT From Baseline to Each Scheduled, Post-Baseline Visit(Baseline to Day 169)
- Percent Change in Plasma AGT From Baseline to Each Scheduled, Post-Baseline Visit(Baseline to Day 169)
- Absolute Level of NT-proBNP(Baseline to Day 169)
- Percent Change from Baseline in NT-proBNP to Each Scheduled, Post-Baseline Visit(Baseline to Day 169)
- Absolute Level of Plasma AGT(Baseline to Day 169)
- Change in NT-proBNP From Baseline to Each Scheduled, Post-Baseline Visit(Baseline to Day 169)
研究者
研究点 (19)
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