A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension
KARDIA-1
A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Multicenter Study to Evaluate the Efficacy and Safety of ALN-AGT01 in Patients With Mild-to-Moderate Hypertension
2 other identifiers
interventional
394
5 countries
75
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hypertension
Started Jul 2021
Typical duration for phase_2 hypertension
75 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 14, 2021
CompletedFirst Posted
Study publicly available on registry
June 23, 2021
CompletedStudy Start
First participant enrolled
July 7, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 4, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 5, 2024
CompletedResults Posted
Study results publicly available
December 27, 2024
CompletedDecember 23, 2025
December 1, 2025
1.7 years
June 14, 2021
October 25, 2024
December 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM
24-hour ABPM was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33, 2. the number of successful nighttime readings were ≥11, 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly mean was the average of BP by each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach.
Baseline and Month 3
Secondary Outcomes (13)
Change From Baseline at Month 3 in Mean Sitting Office SBP
Baseline and Month 3
Change From Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM
Baseline and Month 6
Change From Baseline at Month 6 in Mean Sitting Office SBP
Baseline and Month 6
Percentage of Participants With 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction of ≥20 mmHg From Baseline Without Additional Antihypertensive Medications at Month 6
Month 6
Change From Baseline at Month 3 in 24-hour Mean DBP Assessed by ABPM
Baseline and Month 3
- +8 more secondary outcomes
Study Arms (5)
Placebo
PLACEBO COMPARATORParticipants 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.
Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M)
EXPERIMENTALParticipants 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.
Zilebesiran 300 mg Q6M
EXPERIMENTALParticipants 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.
Zilebesiran 300 mg Q3M
EXPERIMENTALParticipants 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.
Zilebesiran 600 mg Q6M
EXPERIMENTALParticipants 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.
Interventions
Placebo administered by SC injection
ALN-AGT01 administered by SC injection
Eligibility Criteria
You may qualify if:
- Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (75)
Clinical Trial Site
Birmingham, Alabama, 35209, United States
Clinical Trial Site
Tempe, Arizona, 85281, United States
Clinical Trial Site
Tempe, Arizona, 85282, United States
Clinical Trial Site
Beverly Hills, California, 90211, United States
Clinical Trial Site
La Mesa, California, 91942, United States
Clinical Trial Site
Los Angeles, California, 90057, United States
Clinical Trial Site
San Diego, California, 92103, United States
Clinical Trial Site
South Gate, California, 90280, United States
Clinical Trial Site
Vista, California, 92083, United States
Clinical Trial Site
Washington D.C., District of Columbia, 20011, United States
Clinical Trial Site
Clearwater, Florida, 33756, United States
Clinical Trial Site
Coral Gables, Florida, 33134, United States
Clinical Trial Site
Fleming Island, Florida, 32003, United States
Clinical Trial Site
Hollywood, Florida, 33021, United States
Clinical Trial Site
Hollywood, Florida, 33024, United States
Clinical Trial Site
Inverness, Florida, 34452, United States
Clinical Trial Site
Jacksonville, Florida, 32204, United States
Clinical Trial Site
Jacksonville, Florida, 32216, United States
Clinical Trial Site
Jacksonville, Florida, 32256, United States
Clinical Trial Site
Miami, Florida, 33126, United States
Clinical Trial Site
Miami, Florida, 33135, United States
Clinical Trial Site
Naples, Florida, 34102, United States
Clinical Trial Site
Orlando, Florida, 32801, United States
Clinical Trial Site
Acworth, Georgia, 30101, United States
Clinical Trial Site
Columbus, Georgia, 31904, United States
Clinical Trial Site
Fayetteville, Georgia, 30214, United States
Clinical Trial Site
Macon, Georgia, 31210, United States
Clinical Trial Site
Champaign, Illinois, 61822, United States
Clinical Trial Site
Valparaiso, Indiana, 46383, United States
Clinical Trial Site
West Des Moines, Iowa, 50266, United States
Clinical Trial Site
Lake Charles, Louisiana, 70601, United States
Clinical Trial Site
New Orleans, Louisiana, 70124, United States
Clinical Trial Site
Prairieville, Louisiana, 70769, United States
Clinical Trial Site
Baltimore, Maryland, 21229, United States
Clinical Trial Site
Jackson, Mississippi, 39209, United States
Clinical Trial Site
Jefferson City, Missouri, 65109, United States
Clinical Trial Site
Las Vegas, Nevada, 89119, United States
Clinical Trial Site
New York, New York, 10036, United States
Clinical Trial Site
The Bronx, New York, 10456, United States
Clinical Trial Site
Greensboro, North Carolina, 27408, United States
Clinical Trial Site
Greensboro, North Carolina, 27410, United States
Clinical Trial Site
Medford, Oregon, 97504, United States
Clinical Trial Site
Greenville, South Carolina, 29607, United States
Clinical Trial Site
Memphis, Tennessee, 38119, United States
Clinical Trial Site
Cedar Park, Texas, 78613, United States
Clinical Trial Site
Houston, Texas, 77074, United States
Clinical Trial Site
Houston, Texas, 77081, United States
Clinical Trial Site
Magnolia, Texas, 77355, United States
Clinical Trial Site
Pearland, Texas, 77584, United States
Clinical Trial Site
San Antonio, Texas, 78229, United States
Clinical Trial Site
Stephenville, Texas, 76401, United States
Clinical Trial Site
Tomball, Texas, 77375, United States
Clinical Trial Site
Waco, Texas, 76708, United States
Clinical Trial Site
Burke, Virginia, 22015, United States
Clinical Trial Site
Red Deer, Alberta, Canada
Clinical Trial Site
New Minas, Nova Scotia, Canada
Clinical Trial Site
Brampton, Ontario, Canada
Clinical Trial Site
Toronto, Ontario, Canada
Clinical Trial Site
Chicoutimi, Quebec, Canada
Clinical Trial Site
Mirabel, Quebec, Canada
Clinical Trial Site
Montreal, Quebec, Canada
Clinical Trial Site
Québec, Quebec, Canada
Clinical Trial Site
Trois-Rivières, Quebec, Canada
Clinical Trial Site
Victoriaville, Quebec, Canada
Clinical Trial Site
Bayamón, 00961, Puerto Rico
Clinical Trial Site
Ponce, 00716, Puerto Rico
Clinical Trial Site
San Juan, Puerto Rico
Clinical Trial Site
Ivano-Frankivsk, Ukraine
Clinical Trial Site
Kharkiv, Ukraine
Clinical Trial Site
Odesa, Ukraine
Clinical Trial Site
Uzhhorod, Ukraine
Clinical Trial Site
Glasgow, United Kingdom
Clinical Trial Site
Hexham, United Kingdom
Clinical Trial Site
London, United Kingdom
Clinical Trial Site
Manchester, United Kingdom
Related Publications (1)
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.
PMID: 38363577DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Alnylam Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 14, 2021
First Posted
June 23, 2021
Study Start
July 7, 2021
Primary Completion
April 4, 2023
Study Completion
December 5, 2024
Last Updated
December 23, 2025
Results First Posted
December 27, 2024
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
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.