HypertensionPhase 2NCT04083222
A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx
A Phase 2 study testing ISIS 757456 in people with Hypertension, run by Ionis Pharmaceuticals, Inc. at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- 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
- 26 participants
- Where
- 9 sitesUnited States
- Study dates
- 13 Nov 2019to 20 Jul 2020
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion
- 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)
Show all 15Show fewer
- 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
- 12-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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Central Alabama Research
Birmingham, Alabama, 35209
Excel Medical Clinical Trials
Boca Raton, Florida, 33434
Juno Research, LLC
Houston, Texas, 77040
Midwest Institute for Clinical Research
Indianapolis, Indiana, 46260
National Research Institute - Wilshire
Los Angeles, California, 90057
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
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 for 8 Weeks to Hypertensive Subjects With Uncontrolled Blood Pressure
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.
Read the detailed description
This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.
- Conditions
- Hypertension
- Being tested
- Placebo, ISIS 757456
- Keywords
- Hypertension, Hypertensive, AGT, Angiotensinogen, 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
ISIS 757456-matching placebo solution administered as SC injection.
ISIS 757456Drug
ISIS 757456 administered as SC injection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. 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 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.
Measured: 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
Measured: 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
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug
Measured: 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
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
Measured: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start13 Nov 2019
- Primary completion20 Jul 2020
- Study completion20 Jul 2020
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 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
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083222
- Sponsor's protocol ID
- ISIS 757456-CS3
- Status last verified
- Dec 2022
- First submitted
- 6 Sep 2019
- Last updated
- 18 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
Study at a glance
From the registry record, last updated by the sponsor on 18 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 for 8 Weeks to Hypertensive Subjects With Uncontrolled Blood Pressure
- ClinicalTrials.gov ID
- NCT04083222
- Acronym / sponsor ID
- ISIS 757456-CS3
- Conditions
- Hypertension
- Keywords
- Hypertension, Hypertensive, AGT, Angiotensinogen, Blood Pressure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Nov 2019 (actual)
- Primary completion
- 20 Jul 2020 (actual)
- Study completion
- 20 Jul 2020 (actual)
- First posted
- 10 Sep 2019 (actual)
- Results
- Posted 18 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 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.
Detailed description
This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.
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: PlaceboParticipants received ISIS 757456-matching placebo, subcutaneous (SC) injection, once-weekly for 8 weeks and an additional loading dose on Day 3. |
| ISIS 757456 | Experimental | Drug: ISIS 757456Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion
- History of secondary hypertension (HTN)
- 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)
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 |
|---|---|---|
| PlaceboISIS 757456-matching placebo solution administered as SC injection. | Drug | Placebo |
| ISIS 757456ISIS 757456 administered as SC injection. | Drug | ISIS 757456 |
Primary outcome
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo
Time frame: Baseline up to Day 57 (start of Week 9)
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
3 secondary outcomes
Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit
Time frame: 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
Time frame: 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
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 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.
9 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 Hypertension, run by Ionis Pharmaceuticals, Inc. at 9 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 18 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 9 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 18 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 57 Compared to Placebo (time frame: Baseline up to Day 57 (start of Week 9)). 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 NCT04083222, 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 18 Jan 2023.