Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease (ZENITH)

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: High Risk Cardiovascular Disease; Hypertension; High Cardiovascular Risk

Treatments: Drug: Zilebesiran; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07181109

ALN-AGT01-008

2025-522960-34-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 11,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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11,000 participants in 2 patient groups, including a placebo group

Zilebesiran 300 mg

Experimental group

Description:

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

Treatment:

Drug: Zilebesiran

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo