drugset / Trial / NCT05103332

Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)

Phase 2 Completed 663 enrolled Alnylam Pharmaceuticals

RandomizedParallel-groupQuadruple-blindTreatment

Summary

The purpose of this study is to evaluate the effect of zilebesiran on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of zilebesiran as add-on therapy.

Timeline

Start: 2021-11-05
Primary completion: 2023-12-11
Completion: 2024-09-13

Outcome

Met primary endpoint

registry DB Period: Placebo (Add-on to Indapamide) vs DB Period: Zilebesiran (Add-on to Indapamide); p <0.0001; Difference in LS Mean -12.1 NCT05103332 ↗

registry DB Period: Placebo (Add-on to Amlodipine) vs DB Period: Zilebesiran (Add-on to Amlodipine); p <0.0001; Difference in LS Mean -9.7 NCT05103332 ↗

registry DB Period: Placebo (Add-on to Olmesartan) vs DB Period: Zilebesiran (Add-on to Olmesartan); p =0.0183; Difference in LS Mean -4.5 NCT05103332 ↗

release “KARDIA-2 [NCT05103332] Evaluated zilebesiran when added to a standard of care hypertension medication in people with mild to moderate hypertension. Met primary endpoint.” roche.com ↗

release “The KARDIA-2 study achieved its primary endpoint demonstrating clinically and statistically significant additive, placebo-adjusted reductions of up to 12.1 mmHg” alnylam.com ↗

release “KARDIA-2 [NCT05103332] Evaluated zilebesiran when added to a standard of care hypertension medication in people with mild to moderate hypertension. Met primary endpoint” gene.com ↗

Publications

Desai AS, Karns AD, Badariene J, Aswad A, Neutel JM, Kazi F, Park W, Stiglitz D, Makarova N, Havasi A, Zappe DH, Saxena M; KARDIA-2 Study Group. Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial. JAMA. 2025 Jul 1;334(1):46-55. doi: 10.1001/jama.2025.6681.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Zilebesiran	Unknown	600 mg	Subcutaneous
Background	Amlodipine	Other / unclassified	5 mg	—
Background	Indapamide	Small molecule	2.5 mg	—
Background	Olmesartan	Other / unclassified	20 mg	Oral
Background	Olmesartan	Other / unclassified	40 mg	Oral