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.

ALN-AGT01 administered by SC injection

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 blood pressure (BP) by 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.

The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.

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 blood pressure (BP) by each hour of the day. The 24-hour mean was the average of the hourly means.

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 blood pressure (BP) by 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.

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 blood pressure (BP) by 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

The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.

Time adjusted change from baseline in mean sitting office SBP and DBP was the area under the curve (AUC) between Month 1 and 3 visits divided by the duration of time period.

The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach.

Time adjusted change from baseline through Month 6 in 24-hour mean SBP and DBP was determined as the AUC between Month 1 and 6 visits divided by the duration of the time period.

Time adjusted change is the AUC between Month 1 and 6 visits divided by the duration of time period.

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, and 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). Baseline was defined as the last assessment prior to receiving the first dose of study drug. LS mean and SE were calculated using a MMRM approach.

Participants received zilebesiran, 300 mg, as SC injection on Day 1 of the 6-month placebo-controlled DB period. They received placebo at Month 3 of the 6-month placebo-controlled DB period to maintain the blind.

Participants received zilebesiran, 300 mg, as SC injection, Q3M, during the 6-month placebo-controlled DB period.

Participants received zilebesiran, 600 mg, as SC injection, on Day 1 of the 6-month placebo-controlled DB period. They received placebo at Month 3 of the 6-month placebo-controlled DB period to maintain the blind.

Participants who received placebo during the 6-month placebo-controlled DB period were re-randomized at Month 6 to 1 of the 4 initial zilebesiran regimens. Participants in this arm received zilebesiran, 150 mg, as SC injection Q6M after re-randomization for the remainder of the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blind between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received placebo during the 6-month placebo-controlled DB period were re-randomized at Month 6 to 1 of the 4 initial zilebesiran regimens. Participants in this arm received zilebesiran, 300 mg, as SC injection Q6M after re-randomization for the remainder of the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blinding between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received placebo during 6-month placebo-controlled DB period were re-randomized at Month 6 to 1 of the 4 initial zilebesiran regimens. Participants in this arm received zilebesiran, 300 mg, as SC injection Q3M after re-randomization for the remainder of the study.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received placebo 6-month placebo-controlled DB period were re-randomized at Month 6 to 1 of the 4 initial zilebesiran regimens. Participants in this arm received zilebesiran, 600 mg, as SC injection Q6M after re-randomization for the remainder of the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blinding between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received zilebesiran 150 mg Q6M during the 6-month placebo-controlled DB period remained on the same regimen throughout the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blinding between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received zilebesiran 300 mg Q6M during the 6-month placebo-controlled DB period remained on the same regimen throughout the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blinding between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received zilebesiran 300 mg Q3M during the 6-month placebo-controlled DB period remained on the same regimen throughout the study.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.

Participants who received zilebesiran 600 mg Q6M during the 6-month placebo-controlled DB period remained on the same regimen throughout the study. Participants received placebo at the visit where no zilebesiran dose was planned to maintain blinding between the Q3M and Q6M regimens.

Prior to PA6, participants who completed Months 6 to 12 of blinded treatment and pre-dose assessment at Month 12, before a separate OLE study was available, could continue receiving blinded zilebesiran treatment up to additional 24 months in the DB Extension Period. Following PA6, the DB Extension Period was discontinued. Participants who had not yet completed the Month 12 visit at the time of PA6 implementation received their last dose of study drug at Month 9. For participants already in the DB Extension Period at the time of PA6 implementation, dosing depended on scheduled visits: participants whose next visit was at Month 15, 21, 27, or 33 received their planned study drug, while those whose next visit was at Month 18, 24, 30, or 36 did not receive further study drug in the study.