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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04936035 | A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients With Mild To-Moderate Hypertension | PHASE2 | COMPLETED | 394 | — | — | Jul 7, 2021 | Dec 5, 2024 | Dec 23, 2025 | 75 | United States, Canada +3 |
| NCT03934307 | A Study to Evaluate ALN-AGT01 in Patients With Hypertension | PHASE1 | COMPLETED | 124 | — | — | May 1, 2019 | Jan 4, 2023 | Jan 17, 2023 | 3 | United Kingdom |
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.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | 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. |
| Zilebesiran 150 Milligrams (mg) Once Every 6 Months (Q6M) | EXPERIMENTAL | 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. |
| Zilebesiran 300 mg Q6M | EXPERIMENTAL | 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. |
| Zilebesiran 300 mg Q3M | EXPERIMENTAL | 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. |
| Zilebesiran 600 mg Q6M | EXPERIMENTAL | 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. |
| Part A: SAD: ALN-AGT01 | EXPERIMENTAL | Participants will be administered a single dose of ALN-AGT01. |
| Part A: SAD: ALN-AGT01-Matching Placebo | PLACEBO_COMPARATOR | Participants will be administered a single dose of ALN-AGT01-matching placebo. |
| Part B: SD: ALN-AGT01 | EXPERIMENTAL | Participants with controlled salt intake will be administered a single dose of ALN-AGT01. |
| Part B: SD: ALN-AGT01-Matching Placebo | PLACEBO_COMPARATOR | Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo. |
| Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo | EXPERIMENTAL | Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo. |
| Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan | ACTIVE_COMPARATOR | Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan. |
| Part E: Open Label: ALN-AGT01 + Irbesartan | EXPERIMENTAL | Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan. |
| Name | Type | Description |
|---|---|---|
| Placebo | DRUG | Placebo administered by SC injection |
| ALN-AGT01 | DRUG | ALN-AGT01 administered by SC injection |
| ALN-AGT01-Matching Placebo | DRUG | Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC. |
| Irbesartan | DRUG | Irbesartan will be administered orally. |
| Irbesartan-Matching Placebo | DRUG | Irbesartan-matching placebo will be administered orally. |
Inclusion Criteria: * Daytime mean SBP ≥135 mmHg and ≤160 mmHg by ABPM, without antihypertensive medication Exclusion Criteria: * Secondary hypertension, orthostatic hypotension * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2× upper limit of normal (ULN) * Elevated potass...