A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension

General Inclusion Criteria:

1. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), she uses a highly effective contraceptive method. Aged 18 - 75 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent
2. Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m\^2) at screening
3. History of uncontrolled hypertension (HTN) on one or more antihypertensive medications without changes in antihypertensive regimen within 4 weeks of screening and will be required to maintain this regimen throughout the Treatment Period

General Exclusion Criteria:

1. History of secondary 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. 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 ˂ 6 months prior to screening
   • Any hemodynamically unstable atrial or ventricular arrhythmias
   • Significant uncorrected valvular heart disease
   • Any history of stroke or transient ischemic attack \< 6 months prior to screening
3. A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening