Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure (ASTRAAS)

In by ECIR

Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure (ASTRAAS)

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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

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Eligibility

Inclusion Criteria
  1. Males or Females aged 18 to 80 inclusive and weighing ≥ 50 kilograms (kg)
  2. Females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
  3. 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
  4. Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
  5. Must be on a stable regimen of 3 or more antihypertensive medications for at least 1 month and willing 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) non-potassium sparing diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)
Exclusion Criteria
  1. 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
  2. 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)
  3. History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
  4. 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
    • 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 < 1 year prior to screening
  5. A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months
  6. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study
  7. Participant works nighttime shifts (e.g., 11 PM to 7 AM)
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