A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure

NCT ID: NCT04714320

Last Updated: 2025-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-28
• Study Completion Date: 2022-10-03

Brief Summary

The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood pressure, seated automated office SBP, seated automated office diastolic blood pressure (DBP), and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.

Detailed Description

This was a phase 2, double-blind, randomized, placebo-controlled study in up to 160 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study was approximately 31 weeks, which included an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pooled Placebo

Participants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

ISIS 757456 matching placebo administered by SC injection.

IONIS-AGT-LRx 80 mg

Participants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks.

Group Type: EXPERIMENTAL

IONIS-AGT-LRx

Intervention Type: DRUG

IONIS-AGT-LRx administered by SC injection.

IONIS-AGT-LRx 120 mg

Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.

Group Type: EXPERIMENTAL

IONIS-AGT-LRx

Intervention Type: DRUG

IONIS-AGT-LRx administered by SC injection.

Interventions

Placebo

ISIS 757456 matching placebo administered by SC injection.

Intervention Type: DRUG

IONIS-AGT-LRx

IONIS-AGT-LRx administered by SC injection.

Intervention Type: DRUG

Other Intervention Names

ISIS 757456

Eligibility Criteria

Inclusion Criteria

• Males or females aged 18-80 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent
• Females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
• Males must be abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used
• Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
• At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)

Exclusion Criteria

• Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
• History of secondary hypertension (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
• The use of the following at time of screening and during the course of the study:

• Other medications for the treatment of HTN (e.g., minoxidil, diazoxide, renin inhibitors)
• Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement
• Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
• Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
• History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
• 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 ˂ 1 year prior to screening
• Any hemodynamically unstable atrial or ventricular arrhythmias
• Significant uncorrected valvular heart disease
• Any history of stroke or transient ischemic attack < 1 year prior to screening
• A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
• Participant works nighttime shifts (e.g., 11 PM to 7 AM)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pinnacle Research Group

Anniston, Alabama, United States

Central Research Associates, Inc.

Birmingham, Alabama, United States

Achieve Clinical Research, LLC

Birmingham, Alabama, United States

Cahaba Research, Inc.

Pelham, Alabama, United States

Syed Research Consultants LLC

Sheffield, Alabama, United States

Cardiology and Medicine Clinic

Little Rock, Arkansas, United States

Advanced Research Center

Anaheim, California, United States

National Research Institute - Huntington Park

Huntington Park, California, United States

RESPIRE Research

La Mesa, California, United States

Clinical Trials Research

Lincoln, California, United States

Catalina Research Institute

Montclair, California, United States

San Fernando Valley Health Institute

Van Nuys, California, United States

Creekside Endocrine Associates, PC

Denver, Colorado, United States

Chase Medical Research LLC

Waterbury, Connecticut, United States

ALL Medical Research, LLC

Cooper City, Florida, United States

Nature Coast Clinical Research - Crystal River

Crystal River, Florida, United States

East Coast Institute for Research

Jacksonville, Florida, United States

Canvas Clinical Research

Lake Worth, Florida, United States

Allied Biomedical Research Institute, Inc.

Miami, Florida, United States

AMPM Research Clinic

Miami Gardens, Florida, United States

Advanced Research Institute Inc

New Port Richey, Florida, United States

Ocala Research Institute

Ocala, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

Gwinnett Research Institute

Buford, Georgia, United States

Sandhill Research, LLC

Decatur, Georgia, United States

Georgia Institute for Clinical Research

Marietta, Georgia, United States

Eagle Clinical Research

Chicago, Illinois, United States

Clinical Investigation Specialists, Inc. - Wauconda

Wauconda, Illinois, United States

The Research Group of Lexington, LLC

Lexington, Kentucky, United States

Louisiana Heart Center

Slidell, Louisiana, United States

Clinical Trials of America, LLC - Monroe, LA

West Monroe, Louisiana, United States

BioPharm Clinical Research

Caro, Michigan, United States

Palm Research Center, Inc.

Las Vegas, Nevada, United States

NY Scientific

Brooklyn, New York, United States

Summit Research Group, LLC

Stow, Ohio, United States

Conrad Clinical Research

Edmond, Oklahoma, United States

South Oklahoma Heart Research

Oklahoma City, Oklahoma, United States

Health Concepts Research

Rapid City, South Dakota, United States

Chattanooga Research & Medicine, PLLC

Chattanooga, Tennessee, United States

Holston Medical Group

Kingsport, Tennessee, United States

North Texas Research Associates

Allen, Texas, United States

Juno Research, LL

Houston, Texas, United States

Protenium Clinical Research, LLC

Hurst, Texas, United States

Laguna Clinical Research Associates

Laredo, Texas, United States

Kalo Clinical Research

Salt Lake City, Utah, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

York Clinical Research LLC

Norfolk, Virginia, United States

TPMG Clinical Research

Williamsburg, Virginia, United States

Ecogene-21

Chicoutimi, Quebec, Canada

CardioVasc HR

Saint-Jean-sur-Richelieu, Quebec, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ISIS 757456-CS4

Identifier Type: -

Identifier Source: org_study_id