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

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

The purpose of this study is to evaluate the effect of ION904 on plasma angiotensinogen (AGT) in participants with uncontrolled hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: ION904; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Altasciences - Los Angeles
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Sacramento, California, United States, 95821
      • Clinical Trials Research
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
  • Texas
    • Houston, Texas, United States, 77040
      • Juno Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: ION904-CS2; 2022-000140-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No