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

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Hypertension; High Cardiovascular Risk

Treatments: Drug: Placebo; Drug: Zilebesiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT06272487

ALN-AGT01-007

Details and patient eligibility

About

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.

Enrollment: 390 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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390 participants in 2 patient groups, including a placebo group

Zilebesiran

Experimental group

Description:

Participants 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.

Treatment:

Drug: Zilebesiran

Placebo

Placebo Comparator group

Description:

Participants 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.

Treatment:

Drug: Placebo