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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Mild Hypertension

Treatments: Drug: Placebo; Drug: ISIS 757456

Study type: Interventional

Funder types: Industry

Identifiers

NCT03714776

ISIS 757456-CS2

Details and patient eligibility

About

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

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 72 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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25 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

ISIS 757456 80 mg

Experimental group

Description:

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

Treatment:

Drug: ISIS 757456