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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT06272487

Recruitment Status : Recruiting

First Posted : February 22, 2024

Last Update Posted : April 18, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Alnylam Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
High Cardiovascular Risk Hypertension	Drug: Zilebesiran Drug: Placebo	Phase 2

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	390 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Adult Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications
Actual Study Start Date :	February 29, 2024
Estimated Primary Completion Date :	March 20, 2025
Estimated Study Completion Date :	December 19, 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Hypertension

MedlinePlus related topics: Blood Pressure Medicines High Blood Pressure Medicines

Genetic and Rare Diseases Information Center resources: Chronic Graft Versus Host Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Zilebesiran Zilebesiran administered by subcutaneous (SC) injection Other Name: ALN-AGT01
Placebo Comparator: 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.	Drug: Placebo Placebo administered by SC injection

Outcome Measures

Primary Outcome Measures :

Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP) [ Time Frame: Baseline and Month 3 ]

Secondary Outcome Measures :

Change from Baseline at Month 3 in 24-Hour Mean SBP Assessed by Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: Baseline and Month 3 ]
Change from Baseline at Month 6 in Mean Seated Office SBP [ Time Frame: Baseline and Month 6 ]
Change from Baseline at Month 6 in 24-Hour Mean SBP Assessed by ABPM [ Time Frame: Baseline and 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 [ Time Frame: 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 [ Time Frame: Month 6 ]
Change from Baseline at Month 3 and Month 6 in Daytime and Nighttime Mean SBP and Diastolic Blood Pressure (DBP) assessed by ABPM [ Time Frame: Baseline and Months 3 and 6 ]
Change from Baseline at Month 3 and Month 6 in Mean Seated Office DBP [ Time Frame: Baseline and Months 3 and 6 ]
Change from Baseline at Month 3 and Month 6 in 24-hour Mean DBP Assessed by ABPM [ Time Frame: Baseline and Months 3 and 6 ]
Change from Baseline Over Time in Serum Angiotensinogen (AGT) [ Time Frame: Baseline through Month 6 ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 mEq/L

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06272487

Contacts

Layout table for location contacts

Contact: Alnylam Clinical Trial Information Line	1-877-ALNYLAM	clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trial Information Line	1-877-256-9526	clinicaltrials@alnylam.com

Locations

Layout table for location information

United States, Michigan
Clinical Trial Site	Recruiting
Flint, Michigan, United States, 48504

Sponsors and Collaborators

Alnylam Pharmaceuticals

Investigators

Layout table for investigator information

Study Director:	Medical Director	Alnylam Pharmaceuticals

More Information

Layout table for additonal information

Responsible Party:	Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT06272487
Other Study ID Numbers:	ALN-AGT01-007
First Posted:	February 22, 2024 Key Record Dates
Last Update Posted:	April 18, 2024
Last Verified:	April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Alnylam Pharmaceuticals:


High blood pressure Hypertension siRNA Angiotensinogen	AGT Cardiovascular disease Chronic kidney disease Uncontrolled hypertension

Additional relevant MeSH terms:

Layout table for MeSH terms

Hypertension Vascular Diseases Cardiovascular Diseases

To Top