Clinical trial NCT03714776: 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
Official title: A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Subjects With Controlled Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Hypertension
Keywords: Hypertension
Hypertensive
AGT
Angiotensinogen
Blood Pressure
High Blood Pressure
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-22
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo
timeFrame: Baseline, Week 7
Secondary outcomes:
measure: Change From Baseline in the In-clinic Systolic Blood Pressure (SBP) at Days 3, 8, 15, 22, 29, and 36
timeFrame: Baseline, Days 3, 8, 15, 22, 29, and 36
measure: Percent Change From Baseline in Plasma AGT at Days 3, 8, 15, 22, 29 and 36
timeFrame: Baseline, Days 3, 8, 15, 22, 29, and 36
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Lyndhurst
country: United States
facility: Ohio Clinical Research - Lyndhurst
state: Ohio
city: Houston
country: United States
facility: Juno Research, LLC - Northwest Site
state: Texas
city: Norfolk
country: United States
facility: York Clinical Research LLC
state: Virginia
Study officials:
References: