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

Phase 2

Completed

• Conditions: Hypertension
• Interventions: Drug: ISIS 757456; Drug: Placebo

• Registration Number: NCT04083222
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-09-06
• Study First Submitted QC: 2019-09-06
• Study First Posted: 2019-09-10
• Study Start: 2019-11-13
• Primary Completion: 2020-07-20
• Study Completion: 2020-07-20
• Status Verified: 2022-12
• Results First Submitted: 2022-12-21
• Results First Submitted QC: 2022-12-21
• Last Update Submitted: 2022-12-21
• Results First Posted: 2023-01-18
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ISIS 757456	ISIS 757456	Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3.
Placebo	Placebo	Participants received ISIS 757456-matching placebo, subcutaneous (SC) injection, once-weekly for 8 weeks and an additional loading dose on Day 3.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo	Baseline up to Day 57 (start of Week 9)	The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit	Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141
Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit	Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141	The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit	Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141	The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.

Trial Locations

Locations (9)

National Research Institute - Wilshire; 🇺🇸 Los Angeles, California, United States

Midwest Institute for Clinical Research; 🇺🇸 Indianapolis, Indiana, United States

Central Alabama Research; 🇺🇸 Birmingham, Alabama, United States

Orange County Research Center; 🇺🇸 Tustin, California, United States

Excel Medical Clinical Trials; 🇺🇸 Boca Raton, Florida, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States

Ohio Clinical Research - Lyndhurst; 🇺🇸 Lyndhurst, Ohio, United States

Juno Research, LLC; 🇺🇸 Houston, Texas, United States

York Clinical Research LLC; 🇺🇸 Norfolk, Virginia, United States