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

Alnylam Pharmaceuticals394 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

394

Conditions

Hypertension

Interventions

PlaceboDRUG

Placebo administered by SC injection

ALN-AGT01DRUG

ALN-AGT01 administered by SC injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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)

Locations (75)

Outcomes

Primary Outcomes

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.

Time frame: Baseline and Month 3

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline and Month 6

Change From Baseline at Month 6 in Mean Sitting Office SBP

Data from ClinicalTrials.gov

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Clinical Trial Site

Birmingham, Alabama, United States

Clinical Trial Site

Tempe, Arizona, United States

Clinical Trial Site

Tempe, Arizona, United States

Clinical Trial Site

Beverly Hills, California, United States

Clinical Trial Site

La Mesa, California, United States

Clinical Trial Site

Los Angeles, California, United States

Clinical Trial Site

San Diego, California, United States

Clinical Trial Site

South Gate, California, United States

Clinical Trial Site

Vista, California, United States

Clinical Trial Site

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

...and 65 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Baseline and Month 6

Change From Baseline at Month 3 in Mean Sitting Office DBP

Time frame: 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.

Time frame: Baseline and Month 3

Change From Baseline at Month 6 in Mean Sitting Office DBP

Time frame: 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.

Time frame: 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.

Time frame: 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.

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

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