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)

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ClinicalTrials.gov Identifier: NCT06272487

Recruitment Status : Recruiting

First Posted : February 22, 2024

Last Update Posted : May 10, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Alnylam Pharmaceuticals

Tracking Information

First Submitted Date ^ICMJE

February 15, 2024

First Posted Date ^ICMJE

February 22, 2024

Last Update Posted Date

May 10, 2024

Actual Study Start Date ^ICMJE

February 29, 2024

Estimated Primary Completion Date

March 20, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

High Cardiovascular Risk
Hypertension

Intervention ^ICMJE

Drug: Zilebesiran
Zilebesiran administered by subcutaneous (SC) injection

Other Name: ALN-AGT01
Drug: Placebo
Placebo administered by SC injection

Study Arms ^ICMJE

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.

Intervention: Drug: Zilebesiran
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.

Intervention: Drug: Placebo

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

390

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

December 19, 2025

Estimated Primary Completion Date

March 20, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

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

Listed Location Countries ^ICMJE

Canada, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT06272487

Other Study ID Numbers ^ICMJE

ALN-AGT01-007

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

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 United States (US) and/or the European Union (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.

Current Responsible Party

Alnylam Pharmaceuticals

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Alnylam Pharmaceuticals

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Medical Director

Alnylam Pharmaceuticals

PRS Account

Alnylam Pharmaceuticals

Verification Date

May 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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