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

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04083222

Collaborator

(none)

Enrollment

Locations

Arms

8.2

Actual Duration (Months)

2.9

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

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 :

Nov 13, 2019

Actual Primary Completion Date :

Jul 20, 2020

Actual Study Completion Date :

Jul 20, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percent Change in Plasma Angiotensinogen (AGT) from Baseline to Study Day 57 (Study Week 9) Compared to Placebo [Baseline to Week 9]

Secondary Outcome Measures

Change in Systolic Blood Pressure (SBP) from Baseline to Each Scheduled, Post-Baseline Visit [Baseline up to Day 141]
Percent Change in Plasma AGT from Baseline to Each Scheduled, Post-Baseline Visit [Baseline up to Day 141]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Alabama Research	Birmingham	Alabama	United States	35209
2	National Research Institute - Wilshire	Los Angeles	California	United States	90057
3	Orange County Research Center	Tustin	California	United States	92780
4	Excel Medical Clinical Trials	Boca Raton	Florida	United States	33434
5	Progressive Medical Research	Port Orange	Florida	United States	32127
6	Midwest Institute for Clinical Research	Indianapolis	Indiana	United States	46260
7	Ohio Clinical Research - Lyndhurst	Lyndhurst	Ohio	United States	44124
8	Juno Research, LLC	Houston	Texas	United States	77040
9	York Clinical Research LLC	Norfolk	Virginia	United States	23510