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

Phase 2

Active, not recruiting

• Conditions: Hypertension; High Cardiovascular Risk
• Interventions: Drug: Placebo; Drug: Zilebesiran

• Registration Number: NCT06272487
• Lead Sponsor: Alnylam Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-15
• Study First Submitted QC: 2024-02-15
• Study First Posted: 2024-02-22
• Study Start: 2024-02-29
• Primary Completion: 2025-04-02
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-18
• Study Completion: 2025-12-19

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 375

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Zilebesiran	Zilebesiran	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.

Primary Outcome Measures

Name	Time	Method
Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP)	Baseline and Month 3

Secondary Outcome Measures

Name	Time	Method
Change from Baseline at Month 3 and Month 6 in Daytime and Nighttime Mean SBP and Diastolic Blood Pressure (DBP) assessed by ABPM	Baseline and Months 3 and 6
Change from Baseline at Month 6 in 24-Hour Mean SBP Assessed by ABPM	Baseline and Month 6
Change from Baseline at Month 3 in 24-Hour Mean SBP Assessed by Ambulatory Blood Pressure Monitoring (ABPM)	Baseline and Month 3
Change from Baseline at Month 6 in Mean Seated Office SBP	Baseline and Month 6
Change from Baseline at Month 3 and Month 6 in Mean Seated Office DBP	Baseline and Months 3 and 6
Change from Baseline Over Time in Serum Angiotensinogen (AGT)	Baseline through Month 6
Proportion of Patients with Mean Seated Office SBP <140 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6	Month 6
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	Month 6
Change from Baseline at Month 3 and Month 6 in 24-hour Mean DBP Assessed by ABPM	Baseline and Months 3 and 6

Trial Locations

Locations (3)

Clinical Trial Site; 🇬🇧 Pickering, United Kingdom

Clinical Trial Site 1 - Tomball; 🇺🇸 Tomball, Texas, United States

Clinical Trial Site 2 - Tomball; 🇺🇸 Tomball, Texas, United States