Mild HypertensionPhase 2NCT03714776

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

A Phase 2 study testing ISIS 757456 in people with Mild Hypertension, run by Ionis Pharmaceuticals, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 72 years
Conditions the study is for: Mild Hypertension
What is being tested?: ISIS 757456
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 25 participants
Where: 6 sitesUnited States
Study dates: 3 Jan 2019to 13 Nov 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 72 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a participant unsuitable for inclusion
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)

Show all 15Show fewer

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

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Juno Research, LLC - Northwest Site
Houston, Texas, 77040
Midwest Institute for Clinical Research
Indianapolis, Indiana, 46260
Ohio Clinical Research - Lyndhurst
Lyndhurst, Ohio, 44124
York Clinical Research LLC
Norfolk, Virginia, 23510
Progressive Medical Research
Port Orange, Florida, 32127
Orange County Research Center
Tustin, California, 92780

Other trials in United States

About this study

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

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

Read the 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.

Conditions: Mild Hypertension
Being tested: Placebo, ISIS 757456
Keywords: Hypertension, Hypertensive, AGT, Angiotensinogen, Blood Pressure, High Blood Pressure
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo matching solution administered as SC injection.
ISIS 757456Drug
Also called IONIS-AGT-LRx
Administered as SC injection.

Study groups in NCT03714776
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo matching solution injected subcutaneously (SC) once weekly for up to 6 weeks and an additional loading dose on Day 3. Receives: 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. Receives: Drug: ISIS 757456

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo
Measured: 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
Measured: 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
Measured: Baseline, Days 3, 8, 15, 22, 29, and 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Jan 201913 Nov 2019

First posted22 Oct 2018
Study start3 Jan 2019
Primary completion13 Nov 2019
Study completion13 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Mild HypertensionStudies of the same condition, open and under way.
More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03714776
Sponsor's protocol ID: ISIS 757456-CS2
Status last verified: Dec 2022
First submitted: 18 Oct 2018
Last updated: 6 Jan 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Lidani KCF, Trainor PJ, Buscaglia R, Foster K, Jaramillo S, Michael K, Landry AP, Michos ED, Ouyang P, Morgan ES, Tsimikas S, DeFilippis AP. Circulating Levels of Angiotensinogen, Sex Hormones, and Hormone Therapy-The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70083. doi: 10.1111/jch.70083.
PubMed 40556120

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03714776
Acronym / sponsor ID: ISIS 757456-CS2
Conditions: Mild Hypertension
Keywords: Hypertension, Hypertensive, AGT, Angiotensinogen, Blood Pressure, High Blood Pressure
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 3 Jan 2019 (actual)
Primary completion: 13 Nov 2019 (actual)
Study completion: 13 Nov 2019 (actual)
First posted: 22 Oct 2018 (actual)
Results: Posted 6 Jan 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboPlacebo matching solution injected subcutaneously (SC) once weekly for up to 6 weeks and an additional loading dose on Day 3.
ISIS 757456 80 mg	Experimental	Drug: ISIS 757456ISIS 757456 80 mg injected SC once weekly for up to 6 weeks and an additional loading dose of 80 mg on Day 3.

Who may qualify

Ages: 18 to 72 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (15 listed)

Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a participant unsuitable for inclusion
The use of the following at time of screening and during the course of the study:
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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo matching solution administered as SC injection.	Drug	Placebo
ISIS 757456Also: IONIS-AGT-LRxAdministered as SC injection.	Drug	ISIS 757456 80 mg

Primary outcome

Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo
Time frame: Baseline, Week 7

2 secondary outcomes

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

Results and safety

Results posted to the registry on 6 Jan 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	8	8
ISIS 757456 80 mg	17	17

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

Time frame: Baseline, Week 7. Mean (Standard Deviation). Unit: percent change

Measure	Placebo n = 6	ISIS 757456 80 mg n = 15
Value	12.6 (23.3)	-54.2 (24.8)

Placebo vs ISIS 757456 80 mg: p <0.001, ANOVA

Population analysed: PPS included all FAS participants (all randomized participants who received at least 1 injection of study drug and who had at least 1 post-Baseline efficacy or exploratory measurements) who received at least 5 of the 7 doses of the study drug, did not receive antihypertensive medications during the Treatment Period and prior to Day 43, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 19. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 8 (12.5%)	7 of 8 (87.5%)	0 of 8
ISIS 757456 80 mg	0 of 17 (0%)	8 of 17 (47.1%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40556120Lidani KCF, Trainor PJ, Buscaglia R, Foster K, Jaramillo S, Michael K, Landry AP, Michos ED, Ouyang P, Morgan ES, Tsimikas S, DeFilippis AP. Circulating Levels of Angiotensinogen, Sex Hormones, and Hormone Therapy-The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70083. doi: 10.1111/jch.70083.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ISIS 757456 in people with Mild Hypertension, run by Ionis Pharmaceuticals, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 43 (Week 7) Compared to Placebo (time frame: Baseline, Week 7). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03714776, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2023.