HypertensionPhase 2KARDIA-1NCT04936035
A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension
A Phase 2 study testing ALN-AGT01 in people with Hypertension, run by Alnylam Pharmaceuticals at 75 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypertension
- What is being tested?
- ALN-AGT01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 394 participants
- Where
- 75 sitesin 5 countries
- Study dates
- 7 Jul 2021to 5 Dec 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication
Who cannot join
- 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)
Trial locations and contacts
75 sites in 5 countries.
75 sites in 5 countries
United States54 sites
Clinical Trial Site
Acworth, Georgia, 30101
Clinical Trial Site
Baltimore, Maryland, 21229
Clinical Trial Site
Beverly Hills, California, 90211
Clinical Trial Site
Birmingham, Alabama, 35209
Clinical Trial Site
Burke, Virginia, 22015
Clinical Trial Site
Cedar Park, Texas, 78613
Clinical Trial Site
Champaign, Illinois, 61822
Clinical Trial Site
Clearwater, Florida, 33756
Clinical Trial Site
Columbus, Georgia, 31904
Clinical Trial Site
Coral Gables, Florida, 33134
Clinical Trial Site
Fayetteville, Georgia, 30214
Clinical Trial Site
Fleming Island, Florida, 32003
Clinical Trial Site
Greensboro, North Carolina, 27408
Clinical Trial Site
Greensboro, North Carolina, 27410
Clinical Trial Site
Greenville, South Carolina, 29607
Clinical Trial Site
Hollywood, Florida, 33021
Clinical Trial Site
Hollywood, Florida, 33024
Clinical Trial Site
Houston, Texas, 77074
Clinical Trial Site
Houston, Texas, 77081
Clinical Trial Site
Inverness, Florida, 34452
Clinical Trial Site
Jackson, Mississippi, 39209
Clinical Trial Site
Jacksonville, Florida, 32204
Clinical Trial Site
Jacksonville, Florida, 32216
Clinical Trial Site
Jacksonville, Florida, 32256
Clinical Trial Site
Jefferson City, Missouri, 65109
Clinical Trial Site
La Mesa, California, 91942
Clinical Trial Site
Lake Charles, Louisiana, 70601
Clinical Trial Site
Las Vegas, Nevada, 89119
Clinical Trial Site
Los Angeles, California, 90057
Clinical Trial Site
Macon, Georgia, 31210
Clinical Trial Site
Magnolia, Texas, 77355
Clinical Trial Site
Medford, Oregon, 97504
Clinical Trial Site
Memphis, Tennessee, 38119
Clinical Trial Site
Miami, Florida, 33126
Clinical Trial Site
Miami, Florida, 33135
Clinical Trial Site
Naples, Florida, 34102
Clinical Trial Site
New Orleans, Louisiana, 70124
Clinical Trial Site
New York, New York, 10036
Clinical Trial Site
Orlando, Florida, 32801
Clinical Trial Site
Pearland, Texas, 77584
Clinical Trial Site
Prairieville, Louisiana, 70769
Clinical Trial Site
San Antonio, Texas, 78229
Clinical Trial Site
San Diego, California, 92103
Clinical Trial Site
South Gate, California, 90280
Clinical Trial Site
Stephenville, Texas, 76401
Clinical Trial Site
Tempe, Arizona, 85281
Clinical Trial Site
Tempe, Arizona, 85282
Clinical Trial Site
The Bronx, New York, 10456
Clinical Trial Site
Tomball, Texas, 77375
Clinical Trial Site
Valparaiso, Indiana, 46383
Clinical Trial Site
Vista, California, 92083
Clinical Trial Site
Waco, Texas, 76708
Clinical Trial Site
Washington D.C., District of Columbia, 20011
Clinical Trial Site
West Des Moines, Iowa, 50266
Canada10 sites
Clinical Trial Site
Brampton, Ontario
Clinical Trial Site
Chicoutimi, Quebec
Clinical Trial Site
Mirabel, Quebec
Clinical Trial Site
Montreal, Quebec
Clinical Trial Site
New Minas, Nova Scotia
Clinical Trial Site
Québec, Quebec
Clinical Trial Site
Red Deer, Alberta
Clinical Trial Site
Toronto, Ontario
Clinical Trial Site
Trois-Rivières, Quebec
Clinical Trial Site
Victoriaville, Quebec
Ukraine4 sites
Clinical Trial Site
Ivano-Frankivsk
Clinical Trial Site
Kharkiv
Clinical Trial Site
Odesa
Clinical Trial Site
Uzhhorod
United Kingdom4 sites
Clinical Trial Site
Glasgow
Clinical Trial Site
Hexham
Clinical Trial Site
London
Clinical Trial Site
Manchester
Puerto Rico3 sites
Clinical Trial Site
Bayamón, 00961
Clinical Trial Site
Ponce, 00716
Clinical Trial Site
San Juan
About this study
Official title: 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
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.
Read the detailed description
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
- Hypertension
- Being tested
- Placebo, ALN-AGT01
- Keywords
- High blood pressure, Hypertension, Hypertensive, siRNA, Angiotensinogen, AGT
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo administered by SC injection
ALN-AGT01Drug
Also called Zilebesiran
ALN-AGT01 administered by SC injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo; Drug: ALN-AGT01 |
| Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M) | Experimental | 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. Receives: Drug: Placebo; Drug: ALN-AGT01 |
| Zilebesiran 300 mg Q6M | Experimental | 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. Receives: Drug: Placebo; Drug: ALN-AGT01 |
| Zilebesiran 300 mg Q3M | Experimental | 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. Receives: Drug: ALN-AGT01 |
| Zilebesiran 600 mg Q6M | Experimental | 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. Receives: Drug: Placebo; Drug: ALN-AGT01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Month 3
Secondary outcomes (13)
Change From Baseline at Month 3 in Mean Sitting Office SBP
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline and Month 3
Change From Baseline at Month 6 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 blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline and Month 6
Change From Baseline at Month 6 in Mean Sitting Office SBP
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.
Measured: 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
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 blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means.
Measured: Month 6
Change From Baseline at Month 3 in 24-hour Mean DBP 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 blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline and Month 3
Change From Baseline at Month 6 in 24-hour Mean DBP 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 blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach
Measured: Baseline and Month 6
Change From Baseline at Month 3 in Mean Sitting Office DBP
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline and Month 3
Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP
Time adjusted change from baseline in mean sitting office SBP and DBP was the area under the curve (AUC) between Month 1 and 3 visits divided by the duration of time period.
Measured: Baseline and Month 3
Change From Baseline at Month 6 in Mean Sitting Office DBP
The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline and Month 6
Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM
Time adjusted change from baseline through Month 6 in 24-hour mean SBP and DBP was determined as the AUC between Month 1 and 6 visits divided by the duration of the time period.
Measured: Baseline and Month 6
Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP
Time adjusted change is the AUC between Month 1 and 6 visits divided by the duration of time period.
Measured: Baseline and Month 6
Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit
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, and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). Baseline was defined as the last assessment prior to receiving the first dose of study drug. LS mean and SE were calculated using a MMRM approach.
Measured: Baseline, and Months 1, 3 and 6
Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6
Measured: Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2021
- Study start7 Jul 2021
- Primary completion4 Apr 2023
- Study completion5 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04936035
- Sponsor's protocol ID
- ALN-AGT01-002
- Other IDs
- 2021-001248-82
- Acronym
- KARDIA-1
- Status last verified
- Dec 2025
- First submitted
- 14 Jun 2021
- Last updated
- 23 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 38363577