Hypertension| IONIS-AGT-LRx
A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure
This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 150 participants. Participants will be randomized in a 2:1 ratio and will receive a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study will be approximately 29 weeks, which includes an up to 4-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
IONIS-AGT-LRx
Purpose of Study
The purpose of this study is to evaluate the effect of IONIS-AGT-LRx compared to placebo on 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 SBP, diastolic blood pressure (DBP) and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.
Eligibility
Age:
18 - 80Sex:


Key Inclusion / Exclusion Criteria
Inclusion Criteria:
- 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 regimen 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, using a combination of antihypertensive medications in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) non-potassium sparing diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)
Exclusion Criteria:
- Clinically significant abnormalities in screening laboratory results, medical history (e.g., previous acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, type 1 diabetes mellitus)
- 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 (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
- 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 NSAIDs or COX-2 inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
- Potassium sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene)
- History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
- Unstable/underlying 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
- 12-lead electrocardiogram (ECG) demonstrating a QT interval (corrected using Fridericia’s formula [QTcF]) ˃ 450 milliseconds (msec) in males and ˃ 470 msec in females at screening, or a history or evidence of long QT syndrome
- Any hemodynamically unstable atrial or ventricular arrhythmias
- Significant uncorrected valvular heart disease
- Any history of stroke or transient ischemic attack
- A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
- Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
- Participant works nighttime shifts (e.g., 11 PM to 7 AM)
Conditions:
Hypertension
Status:
Recruiting
Phase:
Phase 2
Clinical Trials ID
NCT04714320
Read Detailed Summary:
Start Date / End Date:
04 2021 - 05 2022
Intervention:
IONIS-AGT-LRx
Enrollment:
150