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A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04083222
Recruitment Status : Active, not recruiting
First Posted : September 10, 2019
Last Update Posted : April 29, 2020
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
This study will evaluate the effect of IONIS-AGT-LRx on plasma angiotensinogen (AGT) and systolic blood pressure (SBP) in uncontrolled hypertensive participants who are on two to three antihypertensive medications.

Condition or disease Intervention/treatment Phase
Hypertension Drug: IONIS-AGT-LRx Drug: Placebo Phase 2

Detailed Description:
This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 30 participants. Participants will be randomized in a 2:1 ratio and will receive a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment will last for 8 weeks and the post-treatment period will last for 13 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously for 8 Weeks to Hypertensive Subjects With Uncontrolled Blood Pressure
Actual Study Start Date : November 13, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IONIS-AGT-LRx
IONIS-AGT-LRx administered subcutaneously once-weekly for 8 weeks
Drug: IONIS-AGT-LRx
IONIS-AGT-LRx administered subcutaneously

Placebo Comparator: Placebo
Placebo matching solution administered subcutaneously once-weekly for 8 weeks
Drug: Placebo
Placebo matching IONIS-AGT-LRx solution administered subcutaneously




Primary Outcome Measures :
  1. Percent Change in Plasma Angiotensinogen (AGT) from Baseline to Study Day 57 (Study Week 9) Compared to Placebo [ Time Frame: Baseline to Week 9 ]

Secondary Outcome Measures :
  1. Change in Systolic Blood Pressure (SBP) from Baseline to Each Scheduled, Post-Baseline Visit [ Time Frame: Baseline up to Day 141 ]
  2. Percent Change in Plasma AGT from Baseline to Each Scheduled, Post-Baseline Visit [ Time Frame: Baseline up to Day 141 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion criteria:

  • Males or females aged 18-75 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 surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the participant or participant's non-pregnant female partner must be using a highly effective contraceptive method
  • Body mass index (BMI) ≤ 35.0 kg/square meter (m^2)
  • Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening
  • At screening, the participant must have been on a stable regimen of 2 to 3 antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study, using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), as well as 1 or 2 additional antihypertensive medications in the following categories: beta blocker, acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, pindolol, calcium channel blocker or, non-potassium sparing diuretic

Exclusion Criteria:

  • Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion
  • History of secondary 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., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)
    • Medications that may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
    • Oral or SC anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox)
    • Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol)
    • Phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil)
    • Potassium-sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene)
  • Unstable/underlying cardiovascular disease defined as:

    • Any history of congestive heart failure (New York Heart Association [NYHA] class II-IV)
    • Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening
    • 12-lead electrocardiogram (ECG) corrected using Fridericia's formula (QTcF) > 450 milliseconds (msec) in males and > 470 msec in females at screening, or a history or evidence of long QT syndrome
    • Any clinically significant active atrial or ventricular arrhythmias
    • Any history of coronary bypass or percutaneous coronary intervention

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083222


Locations
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United States, Alabama
Central Alabama Research
Birmingham, Alabama, United States, 35209
United States, California
National Research Institute - Wilshire
Los Angeles, California, United States, 90057
Orange County Research Center
Tustin, California, United States, 92780
United States, Florida
Excel Medical Clinical Trials
Boca Raton, Florida, United States, 33434
Progressive Medical Research
Port Orange, Florida, United States, 32127
United States, Indiana
Midwest Institute for Clinical Research
Indianapolis, Indiana, United States, 46260
United States, Ohio
Ohio Clinical Research - Lyndhurst
Lyndhurst, Ohio, United States, 44124
United States, Texas
Juno Research, LLC
Houston, Texas, United States, 77040
United States, Virginia
York Clinical Research LLC
Norfolk, Virginia, United States, 23510
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04083222    
Other Study ID Numbers: ISIS 757456-CS3
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ionis Pharmaceuticals, Inc.:
Hypertension
Hypertensive
AGT
Angiotensinogen
Blood Pressure
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases