Phase 2
Completed N=663
Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
Source: ClinicalTrials.gov NCT05103332 ↗Enrolled (actual)
663
Serious AEs
1.4%
Results posted
Jul 2025
Primary outcomePrimary: Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data — -3.7; -15.7 mmHg — p=<0.0001
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data |
-3.7; -15.7 | <0.0001 sig |
| PRIMARY Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data |
-0.7; -10.5 | <0.0001 sig |
| PRIMARY Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data |
-3.2; -7.7 | =0.0183 sig |
| SECONDARY Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data |
-0.8; -19.3 | <0.0001 sig |
| SECONDARY Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data |
-4.6; -15.6 | <0.0001 sig |
| SECONDARY Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data |
-4.5; -18.1 | <0.0001 sig |
| SECONDARY 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 |
14.0; 64.2 | <0.0001 sig |
| SECONDARY Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data |
-1.3; -9.1 | — |
| SECONDARY Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data |
-0.2; -10.5 | — |
| SECONDARY Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data |
-2.5; -15.4; -0.9; -8.7 | — |
| SECONDARY Indapamide: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data |
-2.5; -17.2; -0.7; -9.2 | — |
| SECONDARY Indapamide: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data |
-5.8; -16.1; -3.2; -8.0 | — |
| SECONDARY Indapamide: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data |
-7.2; -15.5; -3.6; -7.8 | — |
| SECONDARY Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data |
-2.3; -8.5 | — |
| SECONDARY Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data |
-2.0; -9.5 | — |
| SECONDARY Indapamide: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data |
-1.8; -15.9; -5.3; -15.9; -6.5; -16.4 | — |
| SECONDARY Indapamide: Percent Change From Baseline in Serum Angiotensinogen (AGT) |
6.37; -91.99; 1.90; -92.48; 4.34; -95.50 | — |
| SECONDARY Amlodipine: Change From Baseline at Month 3 in Office SBP - Censored Data |
-1.4; -11.5 | <0.0001 sig |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data |
-1.8; -9.7 | <0.0001 sig |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data |
-2.9; -11.5 | <0.0001 sig |
| SECONDARY 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 |
13.7; 39.8 | <0.0001 sig |
| SECONDARY Amlodipine: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data |
-0.8; -6.6 | — |
| SECONDARY Amlodipine: Change From Baseline at Month 3 in Office DBP - Censored Data |
-1.2; -6.2 | — |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data |
-0.9; -9.9; -0.7; -6.4 | — |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data |
-1.4; -11.3; -0.6; -6.1 | — |
| SECONDARY Amlodipine: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data |
-3.0; -9.0; -1.6; -5.7 | — |
| SECONDARY Amlodipine: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data |
-5.8; -12.6; -3.5; -6.7 | — |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data |
-1.1; -6.2 | — |
| SECONDARY Amlodipine: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data |
-1.4; -6.2 | — |
| SECONDARY Amlodipine: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data |
-2.2; -9.3; -1.3; -11.0; -3.3; -9.1 | — |
| SECONDARY Amlodipine: Percent Change From Baseline in Serum AGT |
2.67; -92.80; 9.62; -95.35; 11.23; -97.45 | — |
| SECONDARY Olmesartan: Change From Baseline at Month 3 in Office SBP - Censored Data |
-2.6; -9.3 | =0.0002 sig |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data |
-5.8; -7.6 | =0.2103 |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data |
-6.3; -10.8 | <0.0001 sig |
| SECONDARY 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 |
17.2; 25.9 | =0.1230 |
| SECONDARY Olmesartan: Change From Baseline at Month 3 in 24-hour Mean DBP, Assessed by ABPM - Censored Data |
-1.4; -3.4 | — |
| SECONDARY Olmesartan: Change From Baseline at Month 3 in Office DBP - Censored Data |
-2.0; -5.3 | — |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data |
-2.2; -5.3; -1.1; -2.3 | — |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline in Office SBP and DBP Through Month 3 - Censored Data |
-2.4; -7.9; -1.2; -3.8 | — |
| SECONDARY Olmesartan: Change From Baseline at Month 6 in 24-hour Mean SBP and DBP, Assessed by ABPM - All Collected Data |
-9.2; -8.3; -5.2; -4.3 | — |
| SECONDARY Olmesartan: Change From Baseline at Month 6 in Office SBP and DBP - All Collected Data |
-11.9; -12.4; -7.0; -7.1 | — |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean DBP, Assessed by ABPM - All Collected Data |
-3.1; -3.5 | — |
| SECONDARY Olmesartan: Time-adjusted Change From Baseline Through Month 6 in Office DBP - All Collected Data |
-3.5; -5.8 | — |
| SECONDARY Olmesartan: Change From Baseline in Daytime and Nighttime SBP and DBP by ABPM at Each Visit - All Collected Data |
-1.0; -3.3; -3.7; -8.5; -8.8; -8.3 | — |
| SECONDARY Olmesartan: Percent Change From Baseline in Serum AGT |
8.08; -87.83; 4.64; -92.61; 4.87; -92.58 | — |
Eligibility Criteria
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)
Data sourced from ClinicalTrials.gov (NCT05103332). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.