Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05103332 | Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2) | PHASE2 | COMPLETED | 663 | — | — | Nov 5, 2021 | Sep 13, 2024 | Nov 3, 2025 | 110 | United States, Canada +6 |
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Indapamide | DRUG | Indapamide administered orally |
| Amlodipine | DRUG | Amlodipine administered orally |
| Olmesartan | DRUG | Olmesartan administered orally |
| Placebo | DRUG | Placebo administered by SC injection |
| Zilebesiran | DRUG | Zilebesiran administered by SC injection |
Inclusion Criteria: * Office SBP at Screening as follows: 1. ≥155 mmHg and ≤180 mmHg for patients with untreated hypertension 2. ≥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 C...