NCT04714320已完成2 期
A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor of Angiotensinogen Production Administered Subcutaneously for 12 Weeks to Hypertensive Patients With Uncontrolled Blood Pressure
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
- 160
- 试验地点
- 50
- 主要终点
- Change From Baseline in Seated Automated Office SBP to Day 85
研究概览
简要总结
The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood pressure, seated automated office SBP, seated automated office diastolic blood pressure (DBP), and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.
详细描述
This was a phase 2, double-blind, randomized, placebo-controlled study in up to 160 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study was approximately 31 weeks, which included an up to 6-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
- None (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
- •Males or females aged 18-80 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent
- •Females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
- •Males must be abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used
- •Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
- •At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)
排除标准
- •Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
- •History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced HTN
- •The use of the following at time of screening and during the course of the study:
- •Other medications for the treatment of HTN (e.g., minoxidil, diazoxide, renin inhibitors)
- •Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement
- •Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
- •Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
- •History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
- •Unstable/underlying known cardiovascular disease defined as:
- •Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV)
- •Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening
- •Any hemodynamically unstable atrial or ventricular arrhythmias
- •Significant uncorrected valvular heart disease
- •Any history of stroke or transient ischemic attack < 1 year prior to screening
- •A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
- •Participant works nighttime shifts (e.g., 11 PM to 7 AM)
研究组 & 干预措施
Pooled Placebo
Placebo Comparator
Participants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks.
干预措施: Placebo (Drug)
IONIS-AGT-LRx 80 mg
Experimental
Participants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks.
干预措施: IONIS-AGT-LRx (Drug)
IONIS-AGT-LRx 120 mg
Experimental
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
干预措施: IONIS-AGT-LRx (Drug)
结局指标
主要结局
Change From Baseline in Seated Automated Office SBP to Day 85
时间窗: Baseline to Day 85
次要结局
- Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit(Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169)
- Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit(Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169)
- Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit(Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169)
- Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit(Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169)
- Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)(Baseline, Day 85)
- Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit(Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169)
- Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit(Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169)
- Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit(Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169)
研究者
研究点 (50)
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