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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.

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 - 80
Sex:
Female Icon + Male Icon

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

Full Details:

https://clinicaltrials.gov/ct2/show/NCT04714320