A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension

NCT ID: NCT04936035

Last Updated: 2024-12-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

394 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-07

Study Completion Date

2024-12-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate the effect of ALN-AGT01 on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of ALN-AGT01.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Participants will receive ALN-AGT01 or placebo for the first 6 months of the 12-month double-blind (DB) treatment period. Participants randomized to placebo will be re-randomized at Month 6 to 1 of the 4 initial ALN-AGT01 regimens until the end of the 12-month DB treatment period. Participants randomized to ALN-AGT01 regimens will remain on their originally assigned regimens through remainder of the study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypertension

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

High blood pressure Hypertension Hypertensive siRNA Angiotensinogen AGT

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo

Participants received zilebesiran matching placebo, subcutaneous (SC) injection, once every 3 months (Q3M), with re-randomization at Month 6 to 1 of the initial 4 zilebesiran regimens. Participants will continue their respective zilebesiran regimen up to Month 12 in the DB period and up to 24 additional months in the DB Extension period. Upon implementation of Amendment 6, the DB Extension period was closed.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo administered by SC injection

ALN-AGT01

Intervention Type DRUG

ALN-AGT01 administered by SC injection

Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M)

Participants receive zilebesiran, 150 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo administered by SC injection

ALN-AGT01

Intervention Type DRUG

ALN-AGT01 administered by SC injection

Zilebesiran 300 mg Q6M

Participants receive zilebesiran, 300 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo administered by SC injection

ALN-AGT01

Intervention Type DRUG

ALN-AGT01 administered by SC injection

Zilebesiran 300 mg Q3M

Participants receive zilebesiran, 300 mg, SC injection, Q3M, during the 12-month DB period. Participants continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Upon implementation of Amendment 6, the DB Extension period was closed.

Group Type EXPERIMENTAL

ALN-AGT01

Intervention Type DRUG

ALN-AGT01 administered by SC injection

Zilebesiran 600 mg Q6M

Participants receive zilebesiran, 600 mg, SC injection, Q6M, during the 12-month DB period. Participants will continue receiving the same zilebesiran regimen for up to 24 additional months in the DB Extension period. Participants in this arm will receive a placebo during those dosing visits when they do not receive zilebesiran to maintain the blind. Upon implementation of Amendment 6, the DB Extension period was closed.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo administered by SC injection

ALN-AGT01

Intervention Type DRUG

ALN-AGT01 administered by SC injection

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Placebo

Placebo administered by SC injection

Intervention Type DRUG

ALN-AGT01

ALN-AGT01 administered by SC injection

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Zilebesiran

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication

Exclusion Criteria

* Secondary hypertension, orthostatic hypotension
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2× upper limit of normal (ULN)
* Elevated potassium \>5 mEq/L
* Estimated glomerular filtration rate (eGFR) of ≤30 mL/min/1.73m\^2
* Received an investigational agent within the last 30 days
* Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, newly diagnosed Type 2 diabetes mellitus
* History of any cardiovascular event within 6 months prior to randomization
* History of intolerance to SC injection(s)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Alnylam Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Alnylam Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Clinical Trial Site

Birmingham, Alabama, United States

Site Status

Clinical Trial Site

Tempe, Arizona, United States

Site Status

Clinical Trial Site

Tempe, Arizona, United States

Site Status

Clinical Trial Site

Beverly Hills, California, United States

Site Status

Clinical Trial Site

La Mesa, California, United States

Site Status

Clinical Trial Site

Los Angeles, California, United States

Site Status

Clinical Trial Site

San Diego, California, United States

Site Status

Clinical Trial Site

South Gate, California, United States

Site Status

Clinical Trial Site

Vista, California, United States

Site Status

Clinical Trial Site

Washington D.C., District of Columbia, United States

Site Status

Clinical Trial Site

Clearwater, Florida, United States

Site Status

Clinical Trial Site

Coral Gables, Florida, United States

Site Status

Clinical Trial Site

Fleming Island, Florida, United States

Site Status

Clinical Trial Site

Hollywood, Florida, United States

Site Status

Clinical Trial Site

Hollywood, Florida, United States

Site Status

Clinical Trial Site

Inverness, Florida, United States

Site Status

Clinical Trial Site

Jacksonville, Florida, United States

Site Status

Clinical Trial Site

Jacksonville, Florida, United States

Site Status

Clinical Trial Site

Jacksonville, Florida, United States

Site Status

Clinical Trial Site

Miami, Florida, United States

Site Status

Clinical Trial Site

Miami, Florida, United States

Site Status

Clinical Trial Site

Naples, Florida, United States

Site Status

Clinical Trial Site

Orlando, Florida, United States

Site Status

Clinical Trial Site

Acworth, Georgia, United States

Site Status

Clinical Trial Site

Columbus, Georgia, United States

Site Status

Clinical Trial Site

Fayetteville, Georgia, United States

Site Status

Clinical Trial Site

Macon, Georgia, United States

Site Status

Clinical Trial Site

Champaign, Illinois, United States

Site Status

Clinical Trial Site

Valparaiso, Indiana, United States

Site Status

Clinical Trial Site

West Des Moines, Iowa, United States

Site Status

Clinical Trial Site

Lake Charles, Louisiana, United States

Site Status

Clinical Trial Site

New Orleans, Louisiana, United States

Site Status

Clinical Trial Site

Prairieville, Louisiana, United States

Site Status

Clinical Trial Site

Baltimore, Maryland, United States

Site Status

Clinical Trial Site

Jackson, Mississippi, United States

Site Status

Clinical Trial Site

Jefferson City, Missouri, United States

Site Status

Clinical Trial Site

Las Vegas, Nevada, United States

Site Status

Clinical Trial Site

New York, New York, United States

Site Status

Clinical Trial Site

The Bronx, New York, United States

Site Status

Clinical Trial Site

Greensboro, North Carolina, United States

Site Status

Clinical Trial Site

Greensboro, North Carolina, United States

Site Status

Clinical Trial Site

Medford, Oregon, United States

Site Status

Clinical Trial Site

Greenville, South Carolina, United States

Site Status

Clinical Trial Site

Memphis, Tennessee, United States

Site Status

Clinical Trial Site

Cedar Park, Texas, United States

Site Status

Clinical Trial Site

Houston, Texas, United States

Site Status

Clinical Trial Site

Houston, Texas, United States

Site Status

Clinical Trial Site

Magnolia, Texas, United States

Site Status

Clinical Trial Site

Pearland, Texas, United States

Site Status

Clinical Trial Site

San Antonio, Texas, United States

Site Status

Clinical Trial Site

Stephenville, Texas, United States

Site Status

Clinical Trial Site

Tomball, Texas, United States

Site Status

Clinical Trial Site

Waco, Texas, United States

Site Status

Clinical Trial Site

Burke, Virginia, United States

Site Status

Clinical Trial Site

Red Deer, Alberta, Canada

Site Status

Clinical Trial Site

New Minas, Nova Scotia, Canada

Site Status

Clinical Trial Site

Brampton, Ontario, Canada

Site Status

Clinical Trial Site

Toronto, Ontario, Canada

Site Status

Clinical Trial Site

Chicoutimi, Quebec, Canada

Site Status

Clinical Trial Site

Mirabel, Quebec, Canada

Site Status

Clinical Trial Site

Montreal, Quebec, Canada

Site Status

Clinical Trial Site

Québec, Quebec, Canada

Site Status

Clinical Trial Site

Trois-Rivières, Quebec, Canada

Site Status

Clinical Trial Site

Victoriaville, Quebec, Canada

Site Status

Clinical Trial Site

Bayamón, , Puerto Rico

Site Status

Clinical Trial Site

Ponce, , Puerto Rico

Site Status

Clinical Trial Site

San Juan, , Puerto Rico

Site Status

Clinical Trial Site

Ivano-Frankivsk, , Ukraine

Site Status

Clinical Trial Site

Kharkiv, , Ukraine

Site Status

Clinical Trial Site

Odesa, , Ukraine

Site Status

Clinical Trial Site

Uzhhorod, , Ukraine

Site Status

Clinical Trial Site

Glasgow, , United Kingdom

Site Status

Clinical Trial Site

Hexham, , United Kingdom

Site Status

Clinical Trial Site

London, , United Kingdom

Site Status

Clinical Trial Site

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Germany United States Canada Puerto Rico Ukraine United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Bakris GL, Saxena M, Gupta A, Chalhoub F, Lee J, Stiglitz D, Makarova N, Goyal N, Guo W, Zappe D, Desai AS; KARDIA-1 Study Group. RNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial. JAMA. 2024 Mar 5;331(9):740-749. doi: 10.1001/jama.2024.0728.

Reference Type DERIVED
PMID: 38363577 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-001248-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALN-AGT01-002

Identifier Type: -

Identifier Source: org_study_id