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

NCT03714776 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ISIS 757456-CS2
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Mild Hypertension

Keywords

Hypertension; Hypertensive; AGT; Angiotensinogen; Blood Pressure; High Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo

  Baseline, Week 7

Secondary Outcomes (2)

• Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36

  Baseline, Days 3, 8, 15, 22, 29, and 36

• Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36

  Baseline, Days 3, 8, 15, 22, 29, and 36

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

ISIS 757456 80 mg

EXPERIMENTAL

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

Drug: ISIS 757456

Interventions

Placebo DRUG

Placebo matching solution administered as SC injection.

Placebo

ISIS 757456 DRUG

Administered as SC injection.

Also known as: IONIS-AGT-LRx

ISIS 757456 80 mg

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
• Body Mass Index (BMI) ≤ 35.0 kg/m2
• Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening
• At Screening, on a stable regimen of antihypertensive medications for at least 1 month prior to screening
• 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

You may not qualify if:

• The use of the following at time of screening and during the course of the study:
• Other medications for the treatment of hypertension (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)
• Medications that also may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
• Oral or subcutaneous anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox)
• Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol)
• Sildenafil, tadalafil, vardenafil
• Unwilling to discontinue antihypertensive mediations during Wash Out (WO) and Treatment Period of study
• Participant has a history of secondary hypertension
• Unstable/underlying cardiovascular disease defined as:
• Any history of congestive heart failure (NYHA class II-IV)
• Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening
• a history or evidence of long QT syndrome
• Any CS active atrial or ventricular arrhythmias
• Any history of coronary bypass or percutaneous coronary intervention

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (6)

Orange County Research Center

Tustin, California, 92780, 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 - Northwest Site

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: October 18, 2018
• First Posted: October 22, 2018
• Study Start: January 3, 2019
• Primary Completion: November 13, 2019
• Study Completion: November 13, 2019
• Last Updated: January 6, 2023
• Results First Posted: January 6, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)