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

NCT04083222 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ISIS 757456-CS3
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 9

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.

Conditions

Hypertension

Keywords

Hypertension; Hypertensive; AGT; Angiotensinogen; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo

  The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.

  Baseline up to Day 57 (start of Week 9)

Secondary Outcomes (3)

• 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

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

ISIS 757456

EXPERIMENTAL

Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3.

Drug: ISIS 757456

Interventions

Placebo DRUG

ISIS 757456-matching placebo solution administered as SC injection.

Placebo

ISIS 757456 DRUG

ISIS 757456 administered as SC injection.

ISIS 757456

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (9)

Central Alabama Research

Birmingham, Alabama, 35209, United States

Location

National Research Institute - Wilshire

Los Angeles, California, 90057, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Excel Medical Clinical Trials

Boca Raton, Florida, 33434, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Midwest Institute for Clinical Research

Indianapolis, Indiana, 46260, United States

Location

Ohio Clinical Research - Lyndhurst

Lyndhurst, Ohio, 44124, United States

Location

Juno Research, LLC

Houston, Texas, 77040, United States

Location

York Clinical Research LLC

Norfolk, Virginia, 23510, United States

Location

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc
• Organization: Ionis Pharmaceuticals, Inc

patients@ionisph.com

800-679-4747

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: September 10, 2019
• Study Start: November 13, 2019
• Primary Completion: July 20, 2020
• Study Completion: July 20, 2020
• Last Updated: January 18, 2023
• Results First Posted: January 18, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)