Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
Phase 2
Completed
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT05103332
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 672
Inclusion Criteria
-
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
Exclusion Criteria
- Secondary hypertension, orthostatic hypotension
- Elevated potassium >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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zilebesiran (Add-on to Olmesartan) Zilebesiran Following a run-in on olmesartan, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the open-label extension (OLE) period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Olmesartan) Placebo Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Olmesartan) Zilebesiran Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Amlodipine) Placebo Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Amlodipine) Zilebesiran Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Indapamide) Placebo Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Indapamide) Zilebesiran Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Zilebesiran (Add-on to Amlodipine) Zilebesiran Following a run-in on amlodipine, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Zilebesiran (Add-on to Indapamide) Zilebesiran Following a run-in on indapamide, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Zilebesiran (Add-on to Olmesartan) Olmesartan Following a run-in on olmesartan, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the open-label extension (OLE) period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Olmesartan) Olmesartan Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Zilebesiran (Add-on to Amlodipine) Amlodipine Following a run-in on amlodipine, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Amlodipine) Amlodipine Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Zilebesiran (Add-on to Indapamide) Indapamide Following a run-in on indapamide, eligible participants will receive zilebesiran on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period. Placebo (Add-on to Indapamide) Indapamide Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants will receive zilebesiran once every 6 months during the open-label extension period. Upon implementation of Amendment 3, the OLE period will be closed and participants will not receive any further treatment with zilebesiran in the OLE period.
- Primary Outcome Measures
Name Time Method Change from Baseline at Month 3 in 24-Hour Mean Systolic Blood Pressure (SBP) Assessed by Ambulatory Blood Pressure Monitoring (ABPM) Baseline and Month 3
- Secondary Outcome Measures
Name Time Method Change from Baseline at Month 3 in Office SBP Baseline and Month 3 Time-adjusted Change from Baseline through Month 6 in Office SBP and 24-hour Mean SBP, Assessed by ABPM Baseline through Month 6 Change in Daytime and Nighttime Mean SBP and DBP, Assessed by ABPM Baseline and Month 6 Daytime is defined as 6 am to 9:59 pm and nighttime is defined as 10 pm to 5:59 am.
Proportion of Patients with 24-hour Mean SBP Assessed by ABPM <130 mmHg and/or Reduction from Baseline ≥ 20 mmHg without Escape Antihypertensive Medication at Month 6 Baseline and Month 6 Change from Baseline in Serum Angiotensinogen (AGT) Baseline through Month 6 Change in 24-hour Mean SBP and Diastolic Blood Pressure (DBP), Assessed by ABPM Baseline and Month 6 Change in Office SBP and DBP Baseline and Month 6
Trial Locations
- Locations (3)
Clinical Trial Site
🇬🇧Torpoint, United Kingdom
Clinical Trials Site
🇺🇸Beverly Hills, California, United States
Clinical Trial site
🇺🇸Winston-Salem, North Carolina, United States