临床试验/NCT05103332

NCT05103332已完成2 期

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication

Alnylam Pharmaceuticals3 个研究点分布在 2 个国家目标入组 663 人开始时间: 2021年11月5日最近更新: 2025年11月3日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方
入组人数: 663
试验地点: 3
主要终点: Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the effect of zilebesiran on systolic and diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety of zilebesiran as add-on therapy.

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

•Office SBP at Screening as follows:
•≥155 mmHg and ≤180 mmHg for patients with untreated hypertension
•≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications
•24-hour mean SBP ≥130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in

排除标准

•Secondary hypertension, orthostatic hypotension
•Elevated potassium <lower limit of normal (LLN) range or >5 milliequivalents per liter (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, or laboratory evidence of diabetes during screening without known diagnosis of diabetes
•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 (Add-on to Indapamide)

Placebo Comparator

Following a 4-week run-in treatment on indapamide, 2.5 milligrams (mg), orally, once daily (QD), eligible participants were randomized to receive placebo matched to zilebesiran as a subcutaneous (SC) injection on Day 1 of 6-month double-blind (DB) treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran once every 6 months (Q6M) during the open-label extension (OLE) period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Indapamide (Drug)

Placebo (Add-on to Indapamide)

Placebo Comparator

干预措施: Placebo (Drug)

Placebo (Add-on to Indapamide)

Placebo Comparator

干预措施: Zilebesiran (Drug)

Zilebesiran (Add-on to Indapamide)

Experimental

Following a 4-week run-in treatment on indapamide, 2.5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Indapamide (Drug)

Zilebesiran (Add-on to Indapamide)

Experimental

干预措施: Zilebesiran (Drug)

Placebo (Add-on to Amlodipine)

Placebo Comparator

Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Amlodipine (Drug)

Placebo (Add-on to Amlodipine)

Placebo Comparator

干预措施: Placebo (Drug)

Placebo (Add-on to Amlodipine)

Placebo Comparator

干预措施: Zilebesiran (Drug)

Zilebesiran (Add-on to Amlodipine)

Experimental

Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Amlodipine (Drug)

Zilebesiran (Add-on to Amlodipine)

Experimental

干预措施: Zilebesiran (Drug)

Placebo (Add-on to Olmesartan)

Placebo Comparator

Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 milliliters per minute [mL/min] at screening enrolled at sites outside of the United States [US] consistent with local labeling), eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Olmesartan (Drug)

Placebo (Add-on to Olmesartan)

Placebo Comparator

干预措施: Placebo (Drug)

Placebo (Add-on to Olmesartan)

Placebo Comparator

干预措施: Zilebesiran (Drug)

Zilebesiran (Add-on to Olmesartan)

Experimental

Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 mL/min at screening enrolled at sites outside of the US consistent with local labeling), eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.

干预措施: Olmesartan (Drug)

Zilebesiran (Add-on to Olmesartan)

Experimental

干预措施: Zilebesiran (Drug)

结局指标

主要结局

Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data

时间窗: Baseline and Month 3

24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). 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 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for 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. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.

Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data

时间窗: Baseline and Month 3

24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). 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 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for 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. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.

Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data

时间窗: Baseline and Month 3

24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). 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 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.

次要结局

Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data(Baseline and Month 3)
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data(Baseline through Month 6)
Indapamide: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6(Month 6)
Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data(Baseline and Month 3)
Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data(Baseline and Month 3)
Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data(Baseline through Month 3)
Indapamide: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data(Baseline through Month 3)
Indapamide: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data(Baseline and Month 6)
Indapamide: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data(Baseline and Month 6)
Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data(Baseline through Month 6)
Indapamide: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data(Baseline, and Month 2, 3 and 6)
Indapamide: Percent Change From Baseline in Serum Angiotensinogen (AGT)(Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6)
Amlodipine: Change From Baseline at Month 3 in Office SBP - Censored Data(Baseline and Month 3)
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data(Baseline through Month 6)
Amlodipine: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6(Month 6)
Amlodipine: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data(Baseline and Month 3)
Amlodipine: Change From Baseline at Month 3 in Office DBP - Censored Data(Baseline and Month 3)
Amlodipine: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data(Baseline through Month 3)
Amlodipine: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data(Baseline through Month 3)
Amlodipine: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data(Baseline and Month 6)
Amlodipine: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data(Baseline and Month 6)
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data(Baseline through Month 6)
Amlodipine: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data(Baseline, and Month 2, 3 and 6)
Amlodipine: Percent Change From Baseline in Serum AGT(Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6)
Olmesartan: Change From Baseline at Month 3 in Office SBP - Censored Data(Baseline and Month 3)
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data(Baseline through Month 6)
Olmesartan: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6(Month 6)
Olmesartan: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data(Baseline and Month 3)
Olmesartan: Change From Baseline at Month 3 in Office DBP - Censored Data(Baseline and Month 3)
Olmesartan: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data(Baseline through Month 3)
Olmesartan: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data(Baseline through Month 3)
Olmesartan: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data(Baseline and Month 6)
Olmesartan: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data(Baseline and Month 6)
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data(Baseline through Month 6)
Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data(Baseline through Month 6)
Olmesartan: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data(Baseline, and Month 2, 3 and 6)
Olmesartan: Percent Change From Baseline in Serum AGT(Baseline, Week 2 and Months 1, 2, 3, 4, 5 and 6)

研究者

发起方

Alnylam Pharmaceuticals

申办方类型

Industry

责任方

Sponsor

研究点 (3)

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