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

Hypertension Clinical Trial

— ASTRAAS  

Official title:

A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor of Angiotensinogen Production Administered Subcutaneously for 12 Weeks to Hypertensive Patients With Uncontrolled Blood Pressure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04714320
• Other study ID #: ISIS 757456-CS4
• Status: Completed
• Phase: Phase 2
• Start date: March 4, 2021
• Est. completion date: September 20, 2022

Study information

• Verified date: February 2023
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is 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.

Description:

This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 150 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 matching placebo. The length of participation in the study will be approximately 31 weeks, which includes an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: September 20, 2022
• Est. primary completion date: September 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 NSAIDs or 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)

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• IONIS-AGT-LRx
Multiple doses of IONIS-AGT-LRx will be administered by SC injection.
• Placebo
IONIS-AGT-LRx-matching placebo will be administered by SC injection.

Locations

Country	Name	City	State
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	CardioVasc HR	Saint-Jean-sur-Richelieu	Quebec
United States	North Texas Research Associates	Allen	Texas
United States	Advanced Research Center	Anaheim	California
United States	Pinnacle Research Group	Anniston	Alabama
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	Central Research Associates, Inc.	Birmingham	Alabama
United States	NY Scientific	Brooklyn	New York
United States	Gwinnett Research Institute	Buford	Georgia
United States	BioPharm Clinical Research	Caro	Michigan
United States	Chattanooga Research & Medicine, PLLC	Chattanooga	Tennessee
United States	Eagle Clinical Research	Chicago	Illinois
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	Nature Coast Clinical Research - Crystal River	Crystal River	Florida
United States	Sandhill Research, LLC	Decatur	Georgia
United States	Creekside Endocrine Associates, PC	Denver	Colorado
United States	Conrad Clinical Research	Edmond	Oklahoma
United States	Juno Research, LL	Houston	Texas
United States	National Research Institute - Huntington Park	Huntington Park	California
United States	Protenium Clinical Research, LLC	Hurst	Texas
United States	East Coast Institute for Research	Jacksonville	Florida
United States	Holston Medical Group	Kingsport	Tennessee
United States	RESPIRE Research	La Mesa	California
United States	Canvas Clinical Research	Lake Worth	Florida
United States	Laguna Clinical Research Associates	Laredo	Texas
United States	Palm Research Center, Inc.	Las Vegas	Nevada
United States	The Research Group of Lexington, LLC	Lexington	Kentucky
United States	Clinical Trials Research	Lincoln	California
United States	Cardiology and Medicine Clinic	Little Rock	Arkansas
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Georgia Institute for Clinical Research	Marietta	Georgia
United States	Allied Biomedical Research Institute, Inc.	Miami	Florida
United States	AMPM Research Clinic	Miami Gardens	Florida
United States	Catalina Research Institute	Montclair	California
United States	Advanced Research Institute Inc	New Port Richey	Florida
United States	York Clinical Research LLC	Norfolk	Virginia
United States	Ocala Research Institute	Ocala	Florida
United States	South Oklahoma Heart Research	Oklahoma City	Oklahoma
United States	Cahaba Research, Inc.	Pelham	Alabama
United States	Progressive Medical Research	Port Orange	Florida
United States	Health Concepts Research	Rapid City	South Dakota
United States	Kalo Clinical Research	Salt Lake City	Utah
United States	Syed Research Consultants LLC	Sheffield	Alabama
United States	Louisiana Heart Center	Slidell	Louisiana
United States	Summit Research Group, LLC	Stow	Ohio
United States	San Fernando Valley Health Institute	Van Nuys	California
United States	Chase Medical Research LLC	Waterbury	Connecticut
United States	Clinical Investigation Specialists, Inc. - Wauconda	Wauconda	Illinois
United States	Clinical Trials of America, LLC - Monroe, LA	West Monroe	Louisiana
United States	TPMG Clinical Research	Williamsburg	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Seated Automated Office Systolic Blood Pressure (SBP) from Baseline to Study Day 85		Baseline to Day 85
Secondary	Change from Baseline in plasma AGT to each scheduled, post-baseline visit		Baseline up to Day 169
Secondary	Change from Baseline to Study Day 85 in 24-hour mean SBP measured by ambulatory blood pressure monitoring (ABPM)		Baseline to Day 85
Secondary	Change from Baseline to Study Day 85 in 24-hour mean Diastolic Blood Pressure (DBP) measured by ABPM		Baseline up to Day 85
Secondary	Percentage of participants reaching the goals of seated automated office seated SBP = 140 mmHg, DBP = 90 mmHg, and both during the study (excluding participants with a baseline SBP of = 140 mmHg)		Up to Day 169
Secondary	Percentage of participants reaching the goals of automated office seated SBP = 130 mmHg, DBP = 80 mmHg, and both during the study		Baseline up to Day 169
Secondary	Change from Baseline on seated automated office SBP to each scheduled, post-Baseline visit		Baseline up to Day 169
Secondary	Change from Baseline on seated automated office DBP to each scheduled, post-Baseline visit		Baseline up to Day 169