A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure
- Registration Number
- NCT04714320
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 160
- 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)
-
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pooled Placebo Placebo Participants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks. IONIS-AGT-LRx 80 mg IONIS-AGT-LRx Participants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks. IONIS-AGT-LRx 120 mg IONIS-AGT-LRx Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Seated Automated Office SBP to Day 85 Baseline to Day 85
- Secondary Outcome Measures
Name Time Method 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 Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 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 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 Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169 Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Trial Locations
- Locations (50)
Nature Coast Clinical Research - Crystal River
🇺🇸Crystal River, Florida, United States
Eagle Clinical Research
🇺🇸Chicago, Illinois, United States
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
Allied Biomedical Research Institute, Inc.
🇺🇸Miami, Florida, United States
Palm Research Center, Inc.
🇺🇸Las Vegas, Nevada, United States
Syed Research Consultants LLC
🇺🇸Sheffield, Alabama, United States
Cardiology and Medicine Clinic
🇺🇸Little Rock, Arkansas, United States
Cahaba Research, Inc.
🇺🇸Pelham, Alabama, United States
Pinnacle Research Group
🇺🇸Anniston, Alabama, United States
ALL Medical Research, LLC
🇺🇸Cooper City, Florida, United States
Protenium Clinical Research, LLC
🇺🇸Hurst, Texas, United States
Kalo Clinical Research
🇺🇸Salt Lake City, Utah, United States
South Oklahoma Heart Research
🇺🇸Oklahoma City, Oklahoma, United States
Central Research Associates, Inc.
🇺🇸Birmingham, Alabama, United States
Creekside Endocrine Associates, PC
🇺🇸Denver, Colorado, United States
Achieve Clinical Research, LLC
🇺🇸Birmingham, Alabama, United States
National Research Institute - Huntington Park
🇺🇸Huntington Park, California, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
East Coast Institute for Research
🇺🇸Jacksonville, Florida, United States
AMPM Research Clinic
🇺🇸Miami Gardens, Florida, United States
Ocala Research Institute
🇺🇸Ocala, Florida, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
York Clinical Research LLC
🇺🇸Norfolk, Virginia, United States
Canvas Clinical Research
🇺🇸Lake Worth, Florida, United States
Advanced Research Center
🇺🇸Anaheim, California, United States
Advanced Research Institute Inc
🇺🇸New Port Richey, Florida, United States
San Fernando Valley Health Institute
🇺🇸Van Nuys, California, United States
RESPIRE Research
🇺🇸La Mesa, California, United States
Chase Medical Research LLC
🇺🇸Waterbury, Connecticut, United States
Summit Research Group, LLC
🇺🇸Stow, Ohio, United States
Georgia Institute for Clinical Research
🇺🇸Marietta, Georgia, United States
Gwinnett Research Institute
🇺🇸Buford, Georgia, United States
Clinical Trials of America, LLC - Monroe, LA
🇺🇸West Monroe, Louisiana, United States
Sandhill Research, LLC
🇺🇸Decatur, Georgia, United States
NY Scientific
🇺🇸Brooklyn, New York, United States
The Research Group of Lexington, LLC
🇺🇸Lexington, Kentucky, United States
Clinical Investigation Specialists, Inc. - Wauconda
🇺🇸Wauconda, Illinois, United States
Louisiana Heart Center
🇺🇸Slidell, Louisiana, United States
Health Concepts Research
🇺🇸Rapid City, South Dakota, United States
BioPharm Clinical Research
🇺🇸Caro, Michigan, United States
Conrad Clinical Research
🇺🇸Edmond, Oklahoma, United States
Juno Research, LL
🇺🇸Houston, Texas, United States
TPMG Clinical Research
🇺🇸Williamsburg, Virginia, United States
Chattanooga Research & Medicine, PLLC
🇺🇸Chattanooga, Tennessee, United States
CardioVasc HR
🇨🇦Saint-Jean-sur-Richelieu, Quebec, Canada
North Texas Research Associates
🇺🇸Allen, Texas, United States
Laguna Clinical Research Associates
🇺🇸Laredo, Texas, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Catalina Research Institute
🇺🇸Montclair, California, United States