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Completed

NCT Number: NCT04936035

A Study to Evaluate 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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Vascular Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinical Trial Site, Red Deer, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Placebo

Drug

Placebo administered by SC injection

ALN-AGT01

Drug

ALN-AGT01 administered by SC injection

Other names: Zilebesiran

Primary outcomes

  1. Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM

    Time frame: Baseline and Month 3

    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.

Secondary outcomes

  1. Change From Baseline at Month 3 in Mean Sitting Office SBP

    Time frame: Baseline and Month 3

    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.

  2. Change From Baseline at Month 6 in 24-hour Mean SBP Assessed by ABPM

    Time frame: Baseline and 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. LS mean and SE were calculated using a MMRM approach.

  3. Change From Baseline at Month 6 in Mean Sitting Office SBP

    Time frame: Baseline and Month 6

    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.

  4. 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

    Time frame: 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.

  5. Change From Baseline at Month 3 in 24-hour Mean DBP Assessed by ABPM

    Time frame: Baseline and Month 3

    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.

  6. Change From Baseline at Month 6 in 24-hour Mean DBP Assessed by ABPM

    Time frame: Baseline and 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. LS mean and SE were calculated using a MMRM approach

  7. Change From Baseline at Month 3 in Mean Sitting Office DBP

    Time frame: Baseline and Month 3

    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.

  8. Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP

    Time frame: Baseline and Month 3

    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.

  9. Change From Baseline at Month 6 in Mean Sitting Office DBP

    Time frame: Baseline and Month 6

    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.

  10. Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM

    Time frame: Baseline and Month 6

    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.

  11. Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP

    Time frame: Baseline and Month 6

    Time adjusted change is the AUC between Month 1 and 6 visits divided by the duration of time period.

  12. Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit

    Time frame: Baseline, and Months 1, 3 and 6

    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.

  13. Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6

    Time frame: Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: KARDIA-1

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Jun 23, 2021
Registry last updated
Dec 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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