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

Phase 2

Completed

• Conditions: Hypertension
• Interventions: Drug: Placebo; Drug: ION904

• Registration Number: NCT05314439
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

Study Timeline

• Study First Submitted: 2022-03-29
• Study First Submitted QC: 2022-03-29
• Study First Posted: 2022-04-06
• Study Start: 2022-04-29
• Primary Completion: 2023-01-31
• Study Completion: 2023-02-15
• Status Verified: 2023-12
• Disposition First Submitted: 2023-12-20
• Last Update Submitted: 2023-12-20
• Disposition First Posted: 2023-12-22
• Last Update Posted: 2023-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Up to 4 monthly doses of placebo will be administered by SC injection.
ION904	ION904	Up to 4 monthly doses of ION904 will be administered by subcutaneous (SC) injection.

Primary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Plasma Angiotensinogen (AGT)	Baseline up to approximately 15 weeks

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (8)

National Research Institute; 🇺🇸 Los Angeles, California, United States

Altasciences; 🇺🇸 Overland Park, Kansas, United States

Altasciences - Los Angeles; 🇺🇸 Cypress, California, United States

ALL Medical Research, LLC; 🇺🇸 Cooper City, Florida, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States

Clinical Trials Research; 🇺🇸 Sacramento, California, United States

NY Scientific; 🇺🇸 Brooklyn, New York, United States

Juno Research, LLC; 🇺🇸 Houston, Texas, United States