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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effect of ION904 on plasma angiotensinogen (AGT) in participants with uncontrolled hypertension.

Detailed Description
-----------------
This is a Phase 2, multicenter, double-blind, randomized, placebo-controlled study. It will include up to approximately 48 participants with mild to moderate hypertension who have uncontrolled blood pressure (˃ 130 - ≤ 170 millimeters of mercury [mmHg] systolic) and have been on one or more anti-hypertensive medications for at least one month. Following an up to 4-week screening period, eligible participants will receive multiple doses of ION904 during a 13-week treatment period, followed by a 13-week post-treatment follow-up period.

Official Title
-----------------
A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of Monthly Subcutaneous Administration of ION904 in Patients With Uncontrolled Hypertension

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: ION904
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
General Inclusion Criteria: 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 Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2) at screening 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: 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 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 A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ION904<br>Up to 4 monthly doses of ION904 will be administered by subcutaneous (SC) injection. | Drug: ION904<br>* ION904 will be administered by SC injection.<br>|
| Placebo Comparator: Placebo<br>Up to 4 monthly doses of placebo will be administered by SC injection. | Drug: Placebo<br>* Placebo will be administered by SC injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Plasma Angiotensinogen (AGT) |  | Baseline up to approximately 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Seated Automated Office Systolic Blood Pressure (SBP) |  | Baseline up to approximately 15 weeks | 
| Change from Baseline in Seated Automated Office Diastolic Blood Pressure (DBP) |  | Baseline up to approximately 15 weeks |