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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 394
- 试验地点
- 1
- 主要终点
- Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: ALN-AGT01 (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: ALN-AGT01 (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: ALN-AGT01 (Drug)
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.
干预措施: ALN-AGT01 (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: ALN-AGT01 (Drug)
结局指标
主要结局
Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM
时间窗: 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.
次要结局
- 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)
- Change From Baseline at Month 6 in 24-hour Mean DBP Assessed by ABPM(Baseline and Month 6)
- Change From Baseline at Month 3 in Mean Sitting Office DBP(Baseline and Month 3)
- Time Adjusted Change From Baseline Through Month 3 in Mean Sitting Office SBP and DBP(Baseline and Month 3)
- Change From Baseline at Month 6 in Mean Sitting Office DBP(Baseline and Month 6)
- Time Adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP and DBP Assessed by ABPM(Baseline and Month 6)
- Time Adjusted Change From Baseline Through Month 6 in Mean Sitting Office SBP and DBP(Baseline and Month 6)
- Change From Baseline in Daytime/Nighttime Mean SBP and DBP Assessed by ABPM at Each Visit(Baseline, and Months 1, 3 and 6)
- Percentage Change From Baseline in Serum Angiotensinogen (AGT) Through Month 6(Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6)