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High Cardiovascular RiskPhase 2KARDIA-3NCT06272487

Zilebesiran as Add-on Therapy in Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications (KARDIA-3)

A Phase 2 study testing Zilebesiran in people with High Cardiovascular Risk and Hypertension, run by Alnylam Pharmaceuticals at 195 sites in 6 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the effect of zilebesiran as add-on therapy in patients with high cardiovascular risk and hypertension not adequately controlled by standard of care antihypertensive medications. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High Cardiovascular Risk, Hypertension
What is being tested?
Zilebesiran
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
375 participants
Where
195 sitesin 6 countries
Study dates
29 Feb 2024to 1 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • History of cardiovascular (CV) disease, high CV risk, or estimated glomerular filtration rate (eGFR) ≥30 to <60 mL/min/1.73m^2
  • Mean seated office SBP ≥140 mmHg and ≤170 mmHg
  • 24-hour mean SBP ≥130 mmHg and ≤170 mmHg assessed by ABPM
  • Must be on stable therapy with 2 to 4 classes of antihypertensive medications

Who cannot join

  • Secondary hypertension
  • Orthostatic hypotension
  • Proteinuria >3 g/day
  • Serum potassium >4.8 milliequivalents per liter (mEq/L)

Trial locations and contacts

195 sites in 6 countries.

195 sites in 6 countries

United States139 sites
  • Clinical Trial Site

    Acworth, Georgia, 30101

  • Clinical Trial Site

    Albuquerque, New Mexico, 87109

  • Clinical Trial Site

    Alexander City, Alabama, 35010

  • Clinical Trial Site

    Atlanta, Georgia, 30322

  • Clinical Trial Site

    Austin, Texas, 78744

  • Clinical Trial Site

    Berlin, New Jersey, 08009

  • Clinical Trial Site

    Bethlehem, Pennsylvania, 18017

  • Clinical Trial Site

    Beverly Hills, California, 90211

  • Clinical Trial Site

    Boise, Idaho, 83706

  • Clinical Trial Site

    Boston, Massachusetts, 02114

  • Clinical Trial Site

    Burke, Virginia, 22015

  • Clinical Trial Site

    Burlington, Vermont, 05401

  • Clinical Trial Site

    Charlotte, North Carolina, 28287

  • Clinical Trial Site

    Chattanooga, Tennessee, 37404

  • Clinical Trial Site

    Chicago, Illinois, 60602

  • Clinical Trial Site

    Clearwater, Florida, 33756

  • Clinical Trial Site

    Cleveland, Ohio, 44106

  • Clinical Trial Site

    Colorado Springs, Colorado, 80918

  • Clinical Trial Site

    Columbus, Georgia, 31904

  • Clinical Trial Site

    Columbus, Mississippi, 39705

  • Clinical Trial Site

    Coppell, Texas, 75019

  • Clinical Trial Site

    Coral Gables, Florida, 33134

  • Clinical Trial Site

    Covina, California, 91723

  • Clinical Trial Site

    Creve Coeur, Missouri, 63141

  • Clinical Trial Site

    Dallas, Texas, 75230

  • Clinical Trial Site

    Dallas, Texas, 75234

  • Clinical Trial Site

    Daphne, Alabama, 36526

  • Clinical Trial Site

    Daytona Beach, Florida, 32117

  • Clinical Trial Site

    Denver, Colorado, 80210

  • Clinical Trial Site

    Denver, Colorado, 80230

  • Clinical Trial Site

    Douglasville, Georgia, 30134

  • Clinical Trial Site

    Durham, North Carolina, 27704

  • Clinical Trial Site

    Durham, North Carolina, 27713

  • Clinical Trial Site

    East Providence, Rhode Island, 02914

  • Clinical Trial Site

    El Dorado, Kansas, 67042

  • Clinical Trial Site

    El Paso, Texas, 79925

  • Clinical Trial Site

    El Paso, Texas, 79935

  • Clinical Trial Site

    Elkhart, Indiana, 46514

  • Clinical Trial Site

    Encinitas, California, 92024

  • Clinical Trial Site

    Evansville, Indiana, 47714

  • Clinical Trial Site

    Flint, Michigan, 48504

  • Clinical Trial Site

    Foley, Alabama, 36535

  • Clinical Trial Site

    Fort Myers, Florida, 33912

  • Clinical Trial Site

    Gainesville, Georgia, 30501

  • Clinical Trial Site

    Garden Grove, California, 92844

  • Clinical Trial Site

    Germantown, Tennessee, 38138

  • Clinical Trial Site

    Gilbert, Arizona, 85297

  • Clinical Trial Site

    Greensboro, North Carolina, 27401

  • Clinical Trial Site

    Greenville, North Carolina, 27834

  • Clinical Trial Site

    Hartford, Connecticut, 06112

  • Clinical Trial Site

    Hollywood, Florida, 33021

  • Clinical Trial Site

    Houston, Texas, 77002

  • Clinical Trial Site

    Houston, Texas, 77024

  • Clinical Trial Site

    Houston, Texas, 77054

  • Clinical Trial Site

    Houston, Texas, 77081

  • Clinical Trial Site

    Houston, Texas, 77099

  • Clinical Trial Site

    Huntington Beach, California, 92647

  • Clinical Trial Site

    Huntsville, Alabama, 35801

  • Clinical Trial Site

    Huntsville, Alabama, 35805

  • Clinical Trial Site

    Jacksonville, Florida, 32204

  • Clinical Trial Site

    Jacksonville, Florida, 32209

  • Clinical Trial Site

    Jacksonville, Florida, 32256

  • Clinical Trial Site

    Jensen Beach, Florida, 34957

  • Clinical Trial Site

    Kalispell, Montana, 59901

  • Clinical Trial Site

    Knoxville, Tennessee, 37909

  • Clinical Trial Site

    Knoxville, Tennessee, 37923

  • Clinical Trial Site

    Lake City, Florida, 32055

  • Clinical Trial Site

    Langhorne, Pennsylvania, 19047

  • Clinical Trial Site

    Las Vegas, Nevada, 89121

  • Clinical Trial Site

    Lincoln, Nebraska, 68510

  • Clinical Trial Site

    Los Angeles, California, 90022

  • Clinical Trial Site

    Los Angeles, California, 90057

  • Clinical Trial Site

    Magnolia, Texas, 77355

  • Clinical Trial Site

    Manassas, Virginia, 20109

  • Clinical Trial Site

    Marion, Ohio, 43302

  • Clinical Trial Site

    Memphis, Tennessee, 38119

  • Clinical Trial Site

    Miami, Florida, 33126

  • Clinical Trial Site

    Miami, Florida, 33135

  • Clinical Trial Site

    Miami, Florida, 33137

  • Clinical Trial Site

    Miami, Florida, 33144

  • Clinical Trial Site

    Miami, Florida, 33155

  • Clinical Trial Site

    Miami, Florida, 33176

  • Clinical Trial Site

    Middlebury, Connecticut, 06762

  • Clinical Trial Site

    Minneapolis, Minnesota, 55404

  • Clinical Trial Site

    Miramar, Florida, 33027

  • Clinical Trial Site

    Monroe, Louisiana, 71201

  • Clinical Trial Site

    Monroe, North Carolina, 28112

  • Clinical Trial Site

    Montgomery, Alabama, 36117

  • Clinical Trial Site

    Myrtle Beach, South Carolina, 29572

  • Clinical Trial Site

    New Orleans, Louisiana, 70119

  • Clinical Trial Site

    New York, New York, 10017

  • Clinical Trial Site

    Newport, Pennsylvania, 17074

  • Clinical Trial Site

    Newton, Kansas, 67114

  • Clinical Trial Site

    Norfolk, Virginia, 23504

  • Clinical Trial Site

    Norman, Oklahoma, 73072

  • Clinical Trial Site

    Northridge, California, 91324

  • Clinical Trial Site

    Northridge, California, 91325

  • Clinical Trial Site

    Oklahoma City, Oklahoma, 73102

  • Clinical Trial Site

    Omaha, Nebraska, 68114

  • Clinical Trial Site

    Orlando, Florida, 32801

  • Clinical Trial Site

    Owensboro, Kentucky, 42303

  • Clinical Trial Site

    Pasadena, California, 91105

  • Clinical Trial Site

    Philadelphia, Pennsylvania, 19114

  • Clinical Trial Site

    Phoenix, Arizona, 85028

  • Clinical Trial Site

    Portsmouth, New Hampshire, 03801

  • Clinical Trial Site

    Raleigh, North Carolina, 27609

  • Clinical Trial Site

    Rapid City, South Dakota, 57701

  • Clinical Trial Site

    Richfield, Minnesota, 55423

  • Clinical Trial Site

    Richmond, Indiana, 47374

  • Clinical Trial Site

    San Antonio, Texas, 78229

  • Clinical Trial Site

    San Antonio, Texas, 78240

  • Clinical Trial Site

    San Diego, California, 92108

  • Clinical Trial Site

    San Diego, California, 92111

  • Clinical Trial Site

    San Dimas, California, 91773

  • Clinical Trial Site

    Savannah, Georgia, 31406

  • Clinical Trial Site

    Shelby, Michigan, 48315

  • Clinical Trial Site

    Shenandoah, Texas, 77384

  • Clinical Trial Site

    Sherman, Texas, 75092

  • Clinical Trial Site

    Simi Valley, California, 93065

  • Clinical Trial Site

    Stephenville, Texas, 76401

  • Clinical Trial Site

    Sun City, Arizona, 85351

  • Clinical Trial Site

    Tempe, Arizona, 85281

  • Clinical Trial Site

    The Villages, Florida, 32162

  • Clinical Trial Site

    Thomasville, Georgia, 31792

  • Clinical Trial Site

    Tomball, Texas, 77375

  • Clinical Trial Site

    Tucson, Arizona, 85741

  • Clinical Trial Site

    Tupelo, Mississippi, 38801

  • Clinical Trial Site

    Vacaville, California, 95687

  • Clinical Trial Site

    Van Nuys, California, 91405

  • Clinical Trial Site

    Washington D.C., District of Columbia, 20009

  • Clinical Trial Site

    Waterbury, Connecticut, 06708

  • Clinical Trial Site

    West Allis, Wisconsin, 53227

  • Clinical Trial Site

    West Hills, California, 91307

  • Clinical Trial Site

    West Springfield, Massachusetts, 01089

  • Clinical Trial Site

    Wichita, Kansas, 67207

  • Clinical Trial Site

    Wilmington, North Carolina, 28403

  • Clinical Trial Site

    Winston-Salem, North Carolina, 27103

  • Clinical Trial Site

    Winter Haven, Florida, 33880

  • Clinical Trial Site

    Ypsilanti, Michigan, 48197

Other trials in United States

United Kingdom24 sites
  • Clinical Trial Site

    Bellshill, ML4 3NJ

  • Clinical Trial Site

    Birmingham, B15 2SQ

  • Clinical Trial Site

    Bristol, BS2 8HW

  • Clinical Trial Site

    Canterbury, CT1 3NG

  • Clinical Trial Site

    Cardiff, CF15 9SS

  • Clinical Trial Site

    Carshalton, SM5 1AA

  • Clinical Trial Site

    Chesterfield, S40 4AA

  • Clinical Trial Site

    Chorley, PR7 7NA

  • Clinical Trial Site

    Fowey, PL23 1DT

  • Clinical Trial Site

    Glasgow, G20 7BE

  • Clinical Trial Site

    Glasgow, G51 4TF

  • Clinical Trial Site

    Hexham, NE46 1QJ

  • Clinical Trial Site

    Leicester, LE5 4PW

  • Clinical Trial Site

    Liskeard, PL14 3XA

  • Clinical Trial Site

    Liverpool, L22 0LG

  • Clinical Trial Site

    London, EC1A 7BE

  • Clinical Trial Site

    London, SE1 1YR

  • Clinical Trial Site

    London, SW17 0QT

  • Clinical Trial Site

    Luton, LU4 0DZ

  • Clinical Trial Site

    Manchester, M15 6SE

  • Clinical Trial Site

    Newquay, TR7 1RU

  • Clinical Trial Site

    Pickering, YO18 8BL

  • Clinical Trial Site

    Plymouth, PL5 3JB

  • Clinical Trial Site

    Torpoint, PL11 2TB

Other trials in United Kingdom

Canada15 sites
  • Clinical Trial Site

    Brampton, L6T 0G1

  • Clinical Trial Site

    Chicoutimi, G7H 7K9

  • Clinical Trial Site

    Greenfield Park, J4V 2G8

  • Clinical Trial Site

    Montreal, H4J 1C5

  • Clinical Trial Site

    Montreal, H4N 2W2

  • Clinical Trial Site

    Québec, G1W 4R4

  • Clinical Trial Site

    Québec, G1V 4T3

  • Clinical Trial Site

    Sainte-Foy, G1V 4G5

  • Clinical Trial Site

    Sarnia, N7T 4X3

  • Clinical Trial Site

    Toronto, M3J 0K2

  • Clinical Trial Site

    Toronto, M4P 1E4

  • Clinical Trial Site

    Toronto, M5B 1W8

  • Clinical Trial Site

    Trois-Rivières, G9A 4P3

  • Clinical Trial Site

    Waterloo, N2T 0C1

  • Clinical Trial Site

    Winnipeg, R2V 3M3

Other trials in Canada

Australia11 sites
  • Clinical Trial Site

    Blacktown, 2148

  • Clinical Trial Site

    Brookvale, 2100

  • Clinical Trial Site

    Bruce, 2617

  • Clinical Trial Site

    Concord, 2139

  • Clinical Trial Site

    Garran, 2605

  • Clinical Trial Site

    Kanwal, 2259

  • Clinical Trial Site

    Kogarah, 2217

  • Clinical Trial Site

    Perth, 6000

  • Clinical Trial Site

    Sippy Downs, 4556

  • Clinical Trial Site

    St Leonards, 2065

  • Clinical Trial Site

    Tarragindi, 4121

Other trials in Australia

Switzerland4 sites
  • Clinical Trial Site

    Basel, 4031

  • Clinical Trial Site

    Geneva, 1205

  • Clinical Trial Site

    Lausanne, 1005

  • Clinical Trial Site

    Lucerne, 6000

Other trials in Switzerland

Puerto Rico2 sites
  • Clinical Trial Site

    Ponce, 00716

  • Clinical Trial Site

    Toa Baja, 00949

Other trials in Puerto Rico

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Adult Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications

The purpose of this study is to evaluate the effect of zilebesiran as add-on therapy in patients with high cardiovascular risk and hypertension not adequately controlled by standard of care antihypertensive medications.

Being tested
Zilebesiran, Placebo
Keywords
High blood pressure, Hypertension, siRNA, Angiotensinogen, AGT, Cardiovascular disease, Chronic kidney disease, Uncontrolled hypertension
Medical subject headings
Hypertension, Cardiovascular Diseases, Renal Insufficiency, Chronic

What participants receive

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

  • ZilebesiranDrug

    Also called ALN-AGT01

    Zilebesiran administered by subcutaneous (SC) injection

  • PlaceboDrug

    Placebo administered by SC injection

Study groups in NCT06272487
Study groupRoleWhat they receive
ZilebesiranExperimentalParticipants will receive zilebesiran on Day 1 of the 6-month double-blind (DB) treatment period. Participants must be on stable doses of at least 2, but not more than 4, antihypertensive medications for at least 30 days prior to screening and plan to remain on stable doses of these medications during screening and through the DB treatment period.
Receives: Drug: Zilebesiran
PlaceboPlacebo comparatorParticipants will receive placebo on Day 1 of the 6-month DB treatment period. Participants must be on stable doses of at least 2, but not more than 4, antihypertensive medications for at least 30 days prior to screening and plan to remain on stable doses of these medications during screening and through the DB treatment period.
Receives: Drug: Placebo

What is being measured

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

  1. Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP)

    Measured: Baseline and Month 3

Secondary outcomes (9)
  1. Change from Baseline at Month 3 in 24-Hour Mean SBP Assessed by Ambulatory Blood Pressure Monitoring (ABPM)

    Measured: Baseline and Month 3

  2. Change from Baseline at Month 6 in Mean Seated Office SBP

    Measured: Baseline and Month 6

  3. Change from Baseline at Month 6 in 24-Hour Mean SBP Assessed by ABPM

    Measured: Baseline and Month 6

  4. Proportion of Patients with Mean Seated Office SBP <140 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6

    Measured: Month 6

  5. Proportion of Patients with 24-hour Mean SBP assessed by ABPM <130 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6

    Measured: Month 6

  6. Change from Baseline at Month 3 and Month 6 in Daytime and Nighttime Mean SBP and Diastolic Blood Pressure (DBP) assessed by ABPM

    Measured: Baseline and Months 3 and 6

  7. Change from Baseline at Month 3 and Month 6 in Mean Seated Office DBP

    Measured: Baseline and Months 3 and 6

  8. Change from Baseline at Month 3 and Month 6 in 24-hour Mean DBP Assessed by ABPM

    Measured: Baseline and Months 3 and 6

  9. Change from Baseline Over Time in Serum Angiotensinogen (AGT)

    Measured: Baseline through Month 6

Timeline

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

  1. First posted22 Feb 2024
  2. Study start29 Feb 2024
  3. Primary completion19 Jun 2025
  4. Study completion1 Dec 2025

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
375 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06272487
Sponsor's protocol ID
ALN-AGT01-007
Acronym
KARDIA-3
Status last verified
Feb 2026
First submitted
15 Feb 2024
Last updated
2 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zilebesiran in people with High Cardiovascular Risk and Hypertension, run by Alnylam Pharmaceuticals at 195 sites in 6 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 4 inclusion and 4 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 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 195 sites in United States, United Kingdom, Canada, Australia, Switzerland and 1 more country. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP) (time frame: Baseline and Month 3). 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 2 Mar 2026.

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