Recruiting
Phase 3

Zilebesiran

Sponsor:

Alnylam Pharmaceuticals

Code:

NCT07181109

Conditions

High Risk Cardiovascular Disease

Hypertension

High Cardiovascular Risk

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zilebesiran

Placebo

Study Details

Brief summary:

The purpose of this study is to evaluate whether zilebesiran versus placebo reduces the risk of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events. This is an event-driven study that will continue until the targeted number of positively adjudicated primary endpoint clinical outcome events (COEs) have been reached.

Conditions

High Risk Cardiovascular Disease

Hypertension

High Cardiovascular Risk

Study ID

NCT07181109

Start date

Sep 22, 2025

Status verified date

Sep, 2026

Completion date

Sep 23, 2030

Anticipated

Primary completion date

Sep 23, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Is 18 years or older for patients with established cardiovascular disease (CVD)
  • Is 55 years or older for patients with high risk for CVD
  • Has established CVD (defined as coronary, cerebrovascular, or peripheral artery disease) or high risk for CVD
  • Has treated hypertension on stable therapy with at least 2 standard of care antihypertensive medications, one of which must be a thiazide, thiazide-like, or loop diuretic

Exclusion Criteria:

  • Has known history of secondary hypertension
  • Has symptomatic orthostatic hypotension
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×upper limit of normal (ULN)
  • Has total serum bilirubin >1.5×ULN
  • Has international normalized ratio (INR) >1.5
  • Has serum potassium >4.8 mEq/L
  • Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m\^2

Study Design

Enrollment

11000 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Zilebesiran 300 mg

Participants will be administered 300 mg zilebesiran subcutaneously (SC) once every 6 months as add-on therapy to their standard of care antihypertensive medications.

placebo comparator: Placebo

Participants will be administered placebo SC once every 6 months as add-on therapy to their standard of care antihypertensive medications.

Interventions

Zilebesiran

Zilebesiran will be administered SC

Placebo

Placebo will be administered SC

Primary outcome measure

  • Time to First Occurrence of a Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Heart Failure (HF) Event (Hospitalization for HF or Urgent HF Visit) [ Time Frame: Up to approximately 5 years ]

Central Contacts and Locations

Central contacts

Clinical Trial Information Line

1-877-ALNYLAMclinicaltrials@alnylam.com

Clinical Trial Information Line

1-877-256-9526clinicaltrials@alnylam.com

Locations

Clinical Trial Site

Recruiting

Birmingham, Alabama, United States, 35205

Clinical Trial Site

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Birmingham, Alabama, United States, 35211

Clinical Trial Site

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Fairhope, Alabama, United States, 36532

Clinical Trial Site

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Foley, Alabama, United States, 36535

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Huntsville, Alabama, United States, 35801

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Huntsville, Alabama, United States, 35805

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Sheffield, Alabama, United States, 35660

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Chandler, Arizona, United States, 85224

Clinical Trial Site

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Gilbert, Arizona, United States, 85296

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Mesa, Arizona, United States, 85213

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Phoenix, Arizona, United States, 85015

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Phoenix, Arizona, United States, 85020

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Sun City, Arizona, United States, 85351

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Sun City West, Arizona, United States, 85375

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Tempe, Arizona, United States, 85283

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Tucson, Arizona, United States, 85715

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Tucson, Arizona, United States, 85741

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Yuma, Arizona, United States, 85364

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Little Rock, Arkansas, United States, 72204

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Little Rock, Arkansas, United States, 72205

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Beverly Hills, California, United States, 90211

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Chula Vista, California, United States, 91910

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Covina, California, United States, 91723

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Escondido, California, United States, 92025

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Glendale, California, United States, 91206

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Huntington Beach, California, United States, 92648

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La Jolla, California, United States, 92037

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Lancaster, California, United States, 93534

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Long Beach, California, United States, 90815

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Lynwood, California, United States, 90262

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Newhall, California, United States, 91321

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Northridge, California, United States, 91325

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Pasadena, California, United States, 91105

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San Diego, California, United States, 92111

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San Dimas, California, United States, 91773

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San Ramon, California, United States, 94583

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Tarzana, California, United States, 91356

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Toluca Lake, California, United States, 91602

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Torrance, California, United States, 90502

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Tustin, California, United States, 92780

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Vista, California, United States, 92081

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Walnut Creek, California, United States, 94598

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Wheat Ridge, Colorado, United States, 80033

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Bridgeport, Connecticut, United States, 06610

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Boca Raton, Florida, United States, 33434

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Brandon, Florida, United States, 33511

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Fleming Island, Florida, United States, 32003

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Fort Lauderdale, Florida, United States, 33308

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Hialeah, Florida, United States, 33012

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Hollywood, Florida, United States, 33024

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Homestead, Florida, United States, 33030

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Jacksonville, Florida, United States, 32205

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Jacksonville, Florida, United States, 32216

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Jensen Beach, Florida, United States, 34957

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Leesburg, Florida, United States, 34748

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Melbourne, Florida, United States, 32934

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Miami, Florida, United States, 33126

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Miami, Florida, United States, 33134

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Miami, Florida, United States, 33135

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Miami, Florida, United States, 33155

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Miami, Florida, United States, 33169

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Miami, Florida, United States, 33186

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Orlando, Florida, United States, 32825

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Palm Springs, Florida, United States, 33406

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Tampa, Florida, United States, 33612

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Tampa, Florida, United States, 33615

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Wellington, Florida, United States, 33449

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Winter Park, Florida, United States, 32789

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Atlanta, Georgia, United States, 30318

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Atlanta, Georgia, United States, 30342

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Brunswick, Georgia, United States, 31520

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Canton, Georgia, United States, 30114

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Columbus, Georgia, United States, 31901

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Columbus, Georgia, United States, 31904

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Conyers, Georgia, United States, 30012

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Conyers, Georgia, United States, 30094

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Fayetteville, Georgia, United States, 30214

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Hinesville, Georgia, United States, 31313

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Johns Creek, Georgia, United States, 30024

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Lawrenceville, Georgia, United States, 30044

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Macon, Georgia, United States, 31201

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Stonecrest, Georgia, United States, 30038

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Suwanee, Georgia, United States, 30024

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Chicago, Illinois, United States, 60640

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Hazel Crest, Illinois, United States, 60429

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Oak Brook, Illinois, United States, 60523

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Orland Park, Illinois, United States, 60462

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Peoria, Illinois, United States, 61636

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Springfield, Illinois, United States, 62701

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Tinley Park, Illinois, United States, 60477

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Avon, Indiana, United States, 46123

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Evansville, Indiana, United States, 47714

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Evansville, Indiana, United States, 47715

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Greenfield, Indiana, United States, 46140

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South Bend, Indiana, United States, 46617

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Valparaiso, Indiana, United States, 46383

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Hutchinson, Kansas, United States, 67502

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Kansas City, Kansas, United States, 66160

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Topeka, Kansas, United States, 66606

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Wichita, Kansas, United States, 67214

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Wichita, Kansas, United States, 67218

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Bowling Green, Kentucky, United States, 42101

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Lexington, Kentucky, United States, 40503

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Versailles, Kentucky, United States, 40383

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Hammond, Louisiana, United States, 70403

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Lafayette, Louisiana, United States, 70503

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New Orleans, Louisiana, United States, 70112

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Opelousas, Louisiana, United States, 70570

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Shreveport, Louisiana, United States, 71105

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Slidell, Louisiana, United States, 70458

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Zachary, Louisiana, United States, 70791

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Baltimore, Maryland, United States, 21229

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Beltsville, Maryland, United States, 20705

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Bowie, Maryland, United States, 20715

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Lanham, Maryland, United States, 20706

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Rockville, Maryland, United States, 20850

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Flint, Michigan, United States, 48504

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Lansing, Michigan, United States, 48912

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Petoskey, Michigan, United States, 49770

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Shelby, Michigan, United States, 48315

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Southfield, Michigan, United States, 48075

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Troy, Michigan, United States, 48085

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Troy, Michigan, United States, 48098

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Richfield, Minnesota, United States, 55423

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Saint Paul, Minnesota, United States, 55102

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Jackson, Mississippi, United States, 39216

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Olive Branch, Mississippi, United States, 38654

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Port Gibson, Mississippi, United States, 39150

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Ridgeland, Mississippi, United States, 39157

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Kansas City, Missouri, United States, 64108

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Kansas City, Missouri, United States, 64111

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Kansas City, Missouri, United States, 64151

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St Louis, Missouri, United States, 63136

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St Louis, Missouri, United States, 63141

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Fremont, Nebraska, United States, 68025

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Omaha, Nebraska, United States, 68114

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Las Vegas, Nevada, United States, 89102

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Las Vegas, Nevada, United States, 89107

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Las Vegas, Nevada, United States, 89121

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Las Vegas, Nevada, United States, 89148

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Portsmouth, New Hampshire, United States, 03801

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Brick, New Jersey, United States, 08724

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Bridgewater, New Jersey, United States, 08807

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Flemington, New Jersey, United States, 08822

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Albuquerque, New Mexico, United States, 87106

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New Windsor, New York, United States, 12553

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North Massapequa, New York, United States, 11758

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Riverhead, New York, United States, 11901

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Rosedale, New York, United States, 11422

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The Bronx, New York, United States, 10461

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West Seneca, New York, United States, 14224

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Westfield, New York, United States, 14787

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Durham, North Carolina, United States, 27704

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Greenville, North Carolina, United States, 27834

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High Point, North Carolina, United States, 27260

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Jacksonville, North Carolina, United States, 28546

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Kings Mountain, North Carolina, United States, 28086

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Monroe, North Carolina, United States, 28112

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Statesville, North Carolina, United States, 28625

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Fargo, North Dakota, United States, 58104

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Beavercreek, Ohio, United States, 45431

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Cincinnati, Ohio, United States, 45212

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Cincinnati, Ohio, United States, 45219

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Columbus, Ohio, United States, 31904

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Columbus, Ohio, United States, 43213

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Dayton, Ohio, United States, 45409

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Lima, Ohio, United States, 45801

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Maumee, Ohio, United States, 43537

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Moraine, Ohio, United States, 45439

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Edmond, Oklahoma, United States, 73013

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Moore, Oklahoma, United States, 73160

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Norman, Oklahoma, United States, 73069

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Oklahoma City, Oklahoma, United States, 73120

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Camp Hill, Pennsylvania, United States, 17701

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Horsham, Pennsylvania, United States, 19044

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Linwood, Pennsylvania, United States, 19061

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Media, Pennsylvania, United States, 19063

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Philadelphia, Pennsylvania, United States, 19114

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Uniontown, Pennsylvania, United States, 15401

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Columbia, South Carolina, United States, 29205

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Greenville, South Carolina, United States, 29607

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Greer, South Carolina, United States, 29650

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Sioux Falls, South Dakota, United States, 57104

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Chattanooga, Tennessee, United States, 37404

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Chattanooga, Tennessee, United States, 37412

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Knoxville, Tennessee, United States, 37909

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Knoxville, Tennessee, United States, 37923

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Allen, Texas, United States, 75013

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Amarillo, Texas, United States, 79106

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Amarillo, Texas, United States, 79124

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Arlington, Texas, United States, 76012

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Arlington, Texas, United States, 76015

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Austin, Texas, United States, 78735

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Austin, Texas, United States, 78759

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Beaumont, Texas, United States, 77702

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Carrollton, Texas, United States, 75006

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Dallas, Texas, United States, 75226

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Dallas, Texas, United States, 75235

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Dallas, Texas, United States, 75246

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Duncanville, Texas, United States, 75137

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El Paso, Texas, United States, 79905

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Euless, Texas, United States, 76040

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Houston, Texas, United States, 77002

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Houston, Texas, United States, 77024

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Houston, Texas, United States, 77025

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Houston, Texas, United States, 77036

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Houston, Texas, United States, 77043

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Houston, Texas, United States, 77061

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Houston, Texas, United States, 77070

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Houston, Texas, United States, 77095

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Houston, Texas, United States, 77429

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Humble, Texas, United States, 77338

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Katy, Texas, United States, 77450

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Kingwood, Texas, United States, 77339

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Laredo, Texas, United States, 78041

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McAllen, Texas, United States, 78503

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McKinney, Texas, United States, 75069

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McKinney, Texas, United States, 75071

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Mesquite, Texas, United States, 75149

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Missouri City, Texas, United States, 77459

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Paris, Texas, United States, 75462

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Pasadena, Texas, United States, 77504

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Plano, Texas, United States, 75024

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Port Arthur, Texas, United States, 77642

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San Antonio, Texas, United States, 78220

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San Antonio, Texas, United States, 78229

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San Antonio, Texas, United States, 78231

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San Antonio, Texas, United States, 78258

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Sherman, Texas, United States, 75092

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Sugar Land, Texas, United States, 77479

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Tomball, Texas, United States, 77375

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Waco, Texas, United States, 76712

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Bountiful, Utah, United States, 84010

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Bountiful, Utah, United States, 84025

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Layton, Utah, United States, 84041

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Arlington, Virginia, United States, 22205

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Danville, Virginia, United States, 24541

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Fairfax, Virginia, United States, 22031

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Falls Church, Virginia, United States, 22042

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Manassas, Virginia, United States, 20109

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Newport News, Virginia, United States, 23606

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Norfolk, Virginia, United States, 23502

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Richmond, Virginia, United States, 23219

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Suffolk, Virginia, United States, 23435

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Winchester, Virginia, United States, 22601

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Bellevue, Washington, United States, 98007

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Kenosha, Wisconsin, United States, 53144

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Brampton, Canada, L6S 0C6

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Brampton, Canada, L6Z 4N5

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Burlington, Canada, L7M 1K9

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Chicoutimi, Canada, G7H 7K9

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Etobicoke, Canada, M8Z 4E4

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Etobicoke, Canada, M9R 4E1

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Greater Sudbury, Canada, P3C 1S8

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Laval, Canada, H7T 2P5

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Lévis, Canada, G6W 0M5

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Longueuil, Canada, J4H 4B9

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Mirabel, Canada, J7J 2K8

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Mississauga, Canada, L5K 2L3

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Moncton, Canada, E1C 2Z3

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Moncton, Canada, E1G 5C4

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Montreal, Canada, H1M 1B1

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Montreal, Canada, H1M 1L3

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Peterborough, Canada, K9J 0B2

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Québec, Canada, G1L 3L5

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Québec, Canada, G1R 2J6

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Québec, Canada, G1V 4G5

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Richmond, Canada, V6V 2X3

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Saint-Jérôme, Canada, J7Z 2V4

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Scarborough, Canada, M1B 4Z8

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Sherbrooke, Canada, 8193462887

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Sydney, Canada, B1S 0K1

More Information

Sponsor

Alnylam Pharmaceuticals

Last update posted

Sep 18, 2026

Last verified

Sep, 2026

Keywords

  • High blood pressure
  • siRNA
  • Angiotensinogen
  • AGT
  • Cardiovascular disease
  • Uncontrolled hypertension
  • RNAi

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-08. This information was provided to ClinicalTrials.gov by Alnylam Pharmaceuticals on 2026-09-18. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.