HypertensionPhase 2ASTRAASNCT04714320
A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure
A Phase 2 study testing IONIS-AGT-LRx in people with Hypertension, run by Ionis Pharmaceuticals, Inc. at 50 sites in 2 countries.
Trial summary
The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- IONIS-AGT-LRx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 50 sitesin 2 countries
- Study dates
- 28 Apr 2021to 3 Oct 2022
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged 18-80 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 abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used
- Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
- At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)
Who cannot join
- Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
- History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced 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., minoxidil, diazoxide, renin inhibitors)
- Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement
- Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
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- Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
- History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
- Unstable/underlying known cardiovascular disease defined as:
- Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV)
- Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening
- Any hemodynamically unstable atrial or ventricular arrhythmias
- Significant uncorrected valvular heart disease
- Any history of stroke or transient ischemic attack < 1 year prior to screening
- A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
- Participant works nighttime shifts (e.g., 11 PM to 7 AM)
Trial locations and contacts
50 sites in 2 countries.
50 sites in 2 countries
United States48 sites
North Texas Research Associates
Allen, Texas, 75013
Advanced Research Center
Anaheim, California, 92805
Pinnacle Research Group
Anniston, Alabama, 36207
Central Research Associates, Inc.
Birmingham, Alabama, 35205
Achieve Clinical Research, LLC
Birmingham, Alabama, 35216
NY Scientific
Brooklyn, New York, 11235
Gwinnett Research Institute
Buford, Georgia, 30519
BioPharm Clinical Research
Caro, Michigan, 48723
Chattanooga Research & Medicine, PLLC
Chattanooga, Tennessee, 37404
Eagle Clinical Research
Chicago, Illinois, 60621
ALL Medical Research, LLC
Cooper City, Florida, 33024
Nature Coast Clinical Research - Crystal River
Crystal River, Florida, 34429
Sandhill Research, LLC
Decatur, Georgia, 30030
Creekside Endocrine Associates, PC
Denver, Colorado, 80246
Conrad Clinical Research
Edmond, Oklahoma, 73013
Juno Research, LL
Houston, Texas, 77040
National Research Institute - Huntington Park
Huntington Park, California, 90255
Protenium Clinical Research, LLC
Hurst, Texas, 76054
East Coast Institute for Research
Jacksonville, Florida, 32216
Holston Medical Group
Kingsport, Tennessee, 37660
RESPIRE Research
La Mesa, California, 91942
Canvas Clinical Research
Lake Worth, Florida, 33467
Laguna Clinical Research Associates
Laredo, Texas, 78041
Palm Research Center, Inc.
Las Vegas, Nevada, 89148
The Research Group of Lexington, LLC
Lexington, Kentucky, 40503
Clinical Trials Research
Lincoln, California, 95648
Cardiology and Medicine Clinic
Little Rock, Arkansas, 72204
Manassas Clinical Research Center
Manassas, Virginia, 20110
Georgia Institute for Clinical Research
Marietta, Georgia, 30060
Allied Biomedical Research Institute, Inc.
Miami, Florida, 33155
AMPM Research Clinic
Miami Gardens, Florida, 33169
Catalina Research Institute
Montclair, California, 91763
Advanced Research Institute Inc
New Port Richey, Florida, 34653
York Clinical Research LLC
Norfolk, Virginia, 23510
Ocala Research Institute
Ocala, Florida, 34471
South Oklahoma Heart Research
Oklahoma City, Oklahoma, 73135
Cahaba Research, Inc.
Pelham, Alabama, 35124
Progressive Medical Research
Port Orange, Florida, 32124
Health Concepts Research
Rapid City, South Dakota, 57702
Kalo Clinical Research
Salt Lake City, Utah, 84102
Syed Research Consultants LLC
Sheffield, Alabama, 35660
Louisiana Heart Center
Slidell, Louisiana, 70458
Summit Research Group, LLC
Stow, Ohio, 44224
San Fernando Valley Health Institute
Van Nuys, California, 91405
Chase Medical Research LLC
Waterbury, Connecticut, 06708
Clinical Investigation Specialists, Inc. - Wauconda
Wauconda, Illinois, 60084
Clinical Trials of America, LLC - Monroe, LA
West Monroe, Louisiana, 71291
TPMG Clinical Research
Williamsburg, Virginia, 23188
Canada2 sites
Ecogene-21
Chicoutimi, Quebec, G7H 7K9
CardioVasc HR
Saint-Jean-sur-Richelieu, Quebec, J3A 1J2
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 of Angiotensinogen Production Administered Subcutaneously for 12 Weeks to Hypertensive Patients With Uncontrolled Blood Pressure
The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood pressure, seated automated office SBP, seated automated office diastolic blood pressure (DBP), and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.
Read the detailed description
This was a phase 2, double-blind, randomized, placebo-controlled study in up to 160 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study was approximately 31 weeks, which included an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
- Conditions
- Hypertension
- Being tested
- Placebo, IONIS-AGT-LRx
- 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 administered by SC injection.
IONIS-AGT-LRxDrug
Also called ISIS 757456
IONIS-AGT-LRx administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Pooled Placebo | Placebo comparator | Participants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks. Receives: Drug: Placebo |
| IONIS-AGT-LRx 80 mg | Experimental | Participants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks. Receives: Drug: IONIS-AGT-LRx |
| IONIS-AGT-LRx 120 mg | Experimental | Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks. Receives: Drug: IONIS-AGT-LRx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Seated Automated Office SBP to Day 85
Measured: Baseline to Day 85
Secondary outcomes (8)
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
Measured: Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Measured: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Measured: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Measured: Baseline, Day 85
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Measured: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Measured: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Measured: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Measured: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2021
- Study start28 Apr 2021
- Primary completion29 Jun 2022
- Study completion3 Oct 2022
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.
- 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
- None (open label)
- Enrolment
- 160 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
- NCT04714320
- Sponsor's protocol ID
- ISIS 757456-CS4
- Acronym
- ASTRAAS
- Status last verified
- Feb 2025
- First submitted
- 14 Jan 2021
- Last updated
- 18 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. 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 of Angiotensinogen Production Administered Subcutaneously for 12 Weeks to Hypertensive Patients With Uncontrolled Blood Pressure
- ClinicalTrials.gov ID
- NCT04714320
- Acronym / sponsor ID
- ASTRAAS / ISIS 757456-CS4
- Conditions
- Hypertension
- Keywords
- Hypertension, Hypertensive, AGT, Angiotensinogen, Blood Pressure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Apr 2021 (actual)
- Primary completion
- 29 Jun 2022 (actual)
- Study completion
- 3 Oct 2022 (actual)
- First posted
- 19 Jan 2021 (actual)
- Results
- Posted 18 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the effect of IONIS-AGT-LRx compared to placebo on seated automated office systolic blood pressure (SBP) from baseline to Study Day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of IONIS-AGT-LRx on ambulatory blood pressure, seated automated office SBP, seated automated office diastolic blood pressure (DBP), and plasma angiotensinogen (AGT) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.
Detailed description
This was a phase 2, double-blind, randomized, placebo-controlled study in up to 160 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or matching placebo. The length of participation in the study was approximately 31 weeks, which included an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pooled Placebo | Placebo comparator | Drug: PlaceboParticipants received ISIS 757456 matching placebo subcutaneously once weekly for 12 weeks. |
| IONIS-AGT-LRx 80 mg | Experimental | Drug: IONIS-AGT-LRxParticipants received ISIS 757456 80 milligrams (mg), subcutaneous (SC) injection, once weekly for 12 weeks. |
| IONIS-AGT-LRx 120 mg | Experimental | Drug: IONIS-AGT-LRxParticipants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males or females aged 18-80 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 abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (WOCBP), a highly effective contraceptive method must be used
- Body mass index (BMI) ≤ 45.0 kilograms per square meter (kg/m^2)
- At screening, the participant must have been on a stable, maximally tolerated regimen (per Investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. The combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine)
Key exclusion criteria (16 listed)
- Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
- History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced HTN
- The use of the following at time of screening and during the course of the study:
- History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
- Unstable/underlying known 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 |
|---|---|---|
| PlaceboISIS 757456 matching placebo administered by SC injection. | Drug | Pooled Placebo |
| IONIS-AGT-LRxAlso: ISIS 757456IONIS-AGT-LRx administered by SC injection. | Drug | IONIS-AGT-LRx 120 mg, IONIS-AGT-LRx 80 mg |
Primary outcome
Change From Baseline in Seated Automated Office SBP to Day 85
Time frame: Baseline to Day 85
8 secondary outcomes
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
Time frame: Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169
Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Time frame: Baseline, Day 85
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Time frame: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Time frame: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
50 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IONIS-AGT-LRx in people with Hypertension, run by Ionis Pharmaceuticals, Inc. at 50 sites in 2 countries.
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 5 inclusion and 16 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 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Canada. 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 Feb 2025). 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?
Change From Baseline in Seated Automated Office SBP to Day 85 (time frame: Baseline to Day 85). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2025.