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

Ionis Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

Hypertension

Treatments

Drug: ISIS 757456

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT04083222

ISIS 757456-CS3

Details and patient eligibility

About

This study evaluated the effect of ISIS 757456 (IONIS-AGT-LRx) on plasma angiotensinogen (AGT) and systolic blood pressure (SBP) in uncontrolled hypertensive participants who were on two to three antihypertensive medications.

Full description

This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received 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 lasted for 8 weeks and the post-treatment period lasted for 13 weeks.

Enrollment

26 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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 hypertension (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