A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Participants With Controlled Blood Pressure

NCT ID: NCT03714776

Last Updated: 2023-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-03
• Study Completion Date: 2019-11-13

Brief Summary

This was a Phase 2, double-blind, randomized, placebo-controlled study of IONIS-AGT-LRx conducted in mild hypertensive participants.

Detailed Description

Participants were randomized in a 2:1 ratio to receive a once-weekly subcutaneous treatment and an additional loading dose on Study Day 3 with either IONIS-AGT-LRx or placebo for 6 weeks.

All participants completed a 13-week Post-Treatment Period.

Conditions

Mild Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo matching solution injected subcutaneously (SC) once weekly for up to 6 weeks and an additional loading dose on Day 3.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching solution administered as SC injection.

ISIS 757456 80 mg

ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.

Group Type: EXPERIMENTAL

ISIS 757456

Intervention Type: DRUG

Administered as SC injection.

Interventions

Placebo

Placebo matching solution administered as SC injection.

Intervention Type: DRUG

ISIS 757456

Administered as SC injection.

Intervention Type: DRUG

Other Intervention Names

IONIS-AGT-LRx

Eligibility Criteria

Inclusion Criteria

1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.

2. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method

3. Body Mass Index (BMI) ≤ 35.0 kg/m2

4. Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening

5. At Screening, on a stable regimen of antihypertensive medications for at least 1 month prior to screening

6. Agree to conduct at home Blood Pressure (BP) and Heart Rate (HR) monitoring three times weekly and document the average of the triplicate measurements assessed on a day in the patient diary

Exclusion Criteria

1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a participant unsuitable for inclusion

2. The use of the following at time of screening and during the course of the study:

1. Other medications for the treatment of hypertension (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)

2. Medications that also may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)

3. Oral or subcutaneous anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox)

4. Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol)

5. Sildenafil, tadalafil, vardenafil

3. Unwilling to discontinue antihypertensive mediations during Wash Out (WO) and Treatment Period of study

4. Participant has a history of secondary hypertension

5. Unstable/underlying cardiovascular disease defined as:

1. Any history of congestive heart failure (NYHA class II-IV)

2. Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening

3. a history or evidence of long QT syndrome

4. Any CS active atrial or ventricular arrhythmias

5. Any history of coronary bypass or percutaneous coronary intervention

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Orange County Research Center

Tustin, California, United States

Progressive Medical Research

Port Orange, Florida, United States

Midwest Institute for Clinical Research

Indianapolis, Indiana, United States

Ohio Clinical Research - Lyndhurst

Lyndhurst, Ohio, United States

Juno Research, LLC - Northwest Site

Houston, Texas, United States

York Clinical Research LLC

Norfolk, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ISIS 757456-CS2

Identifier Type: -

Identifier Source: org_study_id