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

NCT04714320 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ISIS 757456-CS4
• Study Type: interventional
• Target: 160
• Locations: 2 countries
• Sites: 50

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.

Conditions

Hypertension

Keywords

Hypertension; Hypertensive; AGT; Angiotensinogen; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Seated Automated Office SBP to Day 85

  Baseline to Day 85

Secondary Outcomes (8)

• Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit

  Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

• Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit

  Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

• Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit

  Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169

• Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)

  Baseline, Day 85

• Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit

  Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169

Study Arms (3)

Pooled Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

IONIS-AGT-LRx 80 mg

EXPERIMENTAL

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

Drug: IONIS-AGT-LRx

IONIS-AGT-LRx 120 mg

EXPERIMENTAL

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

Drug: IONIS-AGT-LRx

Interventions

Placebo DRUG

ISIS 757456 matching placebo administered by SC injection.

Pooled Placebo

IONIS-AGT-LRx DRUG

IONIS-AGT-LRx administered by SC injection.

Also known as: ISIS 757456

IONIS-AGT-LRx 120 mg; IONIS-AGT-LRx 80 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (50)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Central Research Associates, Inc.

Birmingham, Alabama, 35205, United States

Location

Achieve Clinical Research, LLC

Birmingham, Alabama, 35216, United States

Location

Cahaba Research, Inc.

Pelham, Alabama, 35124, United States

Location

Syed Research Consultants LLC

Sheffield, Alabama, 35660, United States

Location

Cardiology and Medicine Clinic

Little Rock, Arkansas, 72204, United States

Location

Advanced Research Center

Anaheim, California, 92805, United States

Location

National Research Institute - Huntington Park

Huntington Park, California, 90255, United States

Location

RESPIRE Research

La Mesa, California, 91942, United States

Location

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

San Fernando Valley Health Institute

Van Nuys, California, 91405, United States

Location

Creekside Endocrine Associates, PC

Denver, Colorado, 80246, United States

Location

Chase Medical Research LLC

Waterbury, Connecticut, 06708, United States

Location

ALL Medical Research, LLC

Cooper City, Florida, 33024, United States

Location

Nature Coast Clinical Research - Crystal River

Crystal River, Florida, 34429, United States

Location

East Coast Institute for Research

Jacksonville, Florida, 32216, United States

Location

Canvas Clinical Research

Lake Worth, Florida, 33467, United States

Location

Allied Biomedical Research Institute, Inc.

Miami, Florida, 33155, United States

Location

AMPM Research Clinic

Miami Gardens, Florida, 33169, United States

Location

Advanced Research Institute Inc

New Port Richey, Florida, 34653, United States

Location

Ocala Research Institute

Ocala, Florida, 34471, United States

Location

Progressive Medical Research

Port Orange, Florida, 32124, United States

Location

Gwinnett Research Institute

Buford, Georgia, 30519, United States

Location

Sandhill Research, LLC

Decatur, Georgia, 30030, United States

Location

Georgia Institute for Clinical Research

Marietta, Georgia, 30060, United States

Location

Eagle Clinical Research

Chicago, Illinois, 60621, United States

Location

Clinical Investigation Specialists, Inc. - Wauconda

Wauconda, Illinois, 60084, United States

Location

The Research Group of Lexington, LLC

Lexington, Kentucky, 40503, United States

Location

Louisiana Heart Center

Slidell, Louisiana, 70458, United States

Location

Clinical Trials of America, LLC - Monroe, LA

West Monroe, Louisiana, 71291, United States

Location

BioPharm Clinical Research

Caro, Michigan, 48723, United States

Location

Palm Research Center, Inc.

Las Vegas, Nevada, 89148, United States

Location

NY Scientific

Brooklyn, New York, 11235, United States

Location

Summit Research Group, LLC

Stow, Ohio, 44224, United States

Location

Conrad Clinical Research

Edmond, Oklahoma, 73013, United States

Location

South Oklahoma Heart Research

Oklahoma City, Oklahoma, 73135, United States

Location

Health Concepts Research

Rapid City, South Dakota, 57702, United States

Location

Chattanooga Research & Medicine, PLLC

Chattanooga, Tennessee, 37404, United States

Location

Holston Medical Group

Kingsport, Tennessee, 37660, United States

Location

North Texas Research Associates

Allen, Texas, 75013, United States

Location

Juno Research, LL

Houston, Texas, 77040, United States

Location

Protenium Clinical Research, LLC

Hurst, Texas, 76054, United States

Location

Laguna Clinical Research Associates

Laredo, Texas, 78041, United States

Location

Kalo Clinical Research

Salt Lake City, Utah, 84102, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

York Clinical Research LLC

Norfolk, Virginia, 23510, United States

Location

TPMG Clinical Research

Williamsburg, Virginia, 23188, United States

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

CardioVasc HR

Saint-Jean-sur-Richelieu, Quebec, J3A 1J2, Canada

Location

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

globalregulatoryaffairs@ionis.com

760-603-2346

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 19, 2021
• Study Start: April 28, 2021
• Primary Completion: June 29, 2022
• Study Completion: October 3, 2022
• Last Updated: February 18, 2025
• Results First Posted: February 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (48); CA (2)