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

• ClinicalTrials.gov Identifier: NCT05314439
• Recruitment Status: Completed
• First Posted: April 6, 2022
• Last Update Posted: December 22, 2023
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: ION904; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 29, 2022
• Actual Primary Completion Date: January 31, 2023
• Actual Study Completion Date: February 15, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percent Change from Baseline in Plasma Angiotensinogen (AGT) [ Time Frame: Baseline up to approximately 15 weeks ]

Secondary Outcome Measures :

1. Change from Baseline in Seated Automated Office Systolic Blood Pressure (SBP) [ Time Frame: Baseline up to approximately 15 weeks ]
2. Change from Baseline in Seated Automated Office Diastolic Blood Pressure (DBP) [ Time Frame: Baseline up to approximately 15 weeks ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Altasciences - Los Angeles

Cypress, California, United States, 90630

National Research Institute

Los Angeles, California, United States, 90057

Clinical Trials Research

Sacramento, California, United States, 95821

United States, Florida

ALL Medical Research, LLC

Cooper City, Florida, United States, 33024

Progressive Medical Research

Port Orange, Florida, United States, 32127

United States, Kansas

Altasciences

Overland Park, Kansas, United States, 66212

United States, New York

NY Scientific

Brooklyn, New York, United States, 11235

United States, Texas

Juno Research, LLC

Houston, Texas, United States, 77040

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

More Information

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05314439
• Other Study ID Numbers: ION904-CS2; 2022-000140-30 ( EudraCT Number )
• First Posted: April 6, 2022
• Last Update Posted: December 22, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases