Trial Outcomes & Findings for A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (NCT NCT03851705)

NCT ID: NCT03851705

Last Updated: 2023-01-30

Results Overview

Percentage Change in LDL-C levels from Baseline to Day 150

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

56 participants

Primary outcome timeframe

Baseline, Day 150

Results posted on

2023-01-30

Participant Flow

Overall, 56 subjects were enrolled and 53 subjects completed through Day 180 (Part 1) and went into the Open-Label period (Part 2), in which 47 subjects completed.

Participant milestones

Participant milestones
Measure	Part 1 - Inclisiran Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.	Part 1 - Placebo Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 2 - Placebo-Inclisiran Participants who received a dose of 300 mg inclisiran sodium for injection administered by SC injection on Day 270, Day 450 and Day 630. In addition, participants who were assigned to the placebo arm in Part 1 received a dose of 300 mg inclisiran administered by SC injection on Day 180 after completion of Part 1.	Part 2 - Inclisiran-Inclisiran Participants who received a dose of 300 mg inclisiran sodium for injection administered by SC injection on Day 270, Day 450 and Day 630. In addition, participants who were assigned to the placebo arm in Part 1 received a dose of 300 mg inclisiran administered by SC injection on Day 180 after completion of Part 1.
Part 1: Double-Blind Period STARTED	37	19	0	0
Part 1: Double-Blind Period COMPLETED	34	19	0	0
Part 1: Double-Blind Period NOT COMPLETED	3	0	0	0
Part 2: Open-Label Period STARTED	0	0	34	19
Part 2: Open-Label Period COMPLETED	0	0	29	18
Part 2: Open-Label Period NOT COMPLETED	0	0	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 - Inclisiran Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.	Part 2 - Placebo-Inclisiran Participants who received a dose of 300 mg inclisiran sodium for injection administered by SC injection on Day 270, Day 450 and Day 630. In addition, participants who were assigned to the placebo arm in Part 1 received a dose of 300 mg inclisiran administered by SC injection on Day 180 after completion of Part 1.	Part 2 - Inclisiran-Inclisiran Participants who received a dose of 300 mg inclisiran sodium for injection administered by SC injection on Day 270, Day 450 and Day 630. In addition, participants who were assigned to the placebo arm in Part 1 received a dose of 300 mg inclisiran administered by SC injection on Day 180 after completion of Part 1.
Part 1: Double-Blind Period Withdrawal by Subject	2	0	0
Part 1: Double-Blind Period Other reason	1	0	0
Part 2: Open-Label Period Other reason	0	0	1
Part 2: Open-Label Period Death	0	3	0
Part 2: Open-Label Period Withdrawal by Subject	0	2	0

Baseline Characteristics

A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inclisiran n=37 Participants Participants who received a dose of inclisiran sodium for injection administered by sub-cutaneous (SC) injection	Placebo n=19 Participants Participants who received a dose of placebo administered by sub-cutaneous (SC) injection	Total n=56 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=99 Participants	19 Participants n=107 Participants	53 Participants n=206 Participants
Age, Categorical >=65 years	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Sex: Female, Male Female	23 Participants n=99 Participants	11 Participants n=107 Participants	34 Participants n=206 Participants
Sex: Female, Male Male	14 Participants n=99 Participants	8 Participants n=107 Participants	22 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	6 Participants n=99 Participants	2 Participants n=107 Participants	8 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	31 Participants n=99 Participants	17 Participants n=107 Participants	48 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in LDL-C levels from Baseline to Day 150

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150	2.39 Percentage change Interval -19.98 to 24.75	0.70 Percentage change Interval -14.03 to 15.44

SECONDARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in LDL-C levels (mg/dL) from baseline to Day 150

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150	-8.82 mg/dL Interval -75.19 to 57.55	-2.35 mg/dL Interval -36.34 to 31.63

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in LDL-C levels from baseline to subsequent visits on Days 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	3.3 Percentage change Interval -13.0 to 19.6	-8.7 Percentage change Interval -20.3 to 2.8
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-1.5 Percentage change Interval -17.0 to 14.1	-7.2 Percentage change Interval -19.0 to 4.6
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	-2.9 Percentage change Interval -22.6 to 16.9	1.8 Percentage change Interval -12.5 to 16.1

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.

Percentage Change in LDL-C levels from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 270	-10.1 Percentage change Standard Deviation 41.62	-9.1 Percentage change Standard Deviation 33.99
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	-14.4 Percentage change Standard Deviation 32.62	-4.8 Percentage change Standard Deviation 50.45
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	-6.7 Percentage change Standard Deviation 26.69	-4.7 Percentage change Standard Deviation 46.92
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	-9.3 Percentage change Standard Deviation 29.52	2.4 Percentage change Standard Deviation 61.70
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-16.6 Percentage change Standard Deviation 20.45	-6.6 Percentage change Standard Deviation 43.75
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-8.7 Percentage change Standard Deviation 32.17	-4.2 Percentage change Standard Deviation 42.39
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-14.6 Percentage change Standard Deviation 26.11	-6.2 Percentage change Standard Deviation 47.29

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute change in LDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150 and 180 based on the

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	3.6 mg/dL Interval -39.6 to 46.8	-16.3 mg/dL Interval -47.0 to 14.4
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	-17.2 mg/dL Interval -70.8 to 36.3	0.5 mg/dL Interval -38.3 to 39.2
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-7.0 mg/dL Interval -50.5 to 36.4	-14.5 mg/dL Interval -47.5 to 18.5

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	-12.3 mg/dL Standard Deviation 108.49	-19.8 mg/dL Standard Deviation 111.41
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	-20.9 mg/dL Standard Deviation 118.05	-2.2 mg/dL Standard Deviation 127.13
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-50.5 mg/dL Standard Deviation 70.47	-14.9 mg/dL Standard Deviation 107.90
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-27.9 mg/dL Standard Deviation 115.46	-8.6 mg/dL Standard Deviation 112.93
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-43.5 mg/dL Standard Deviation 92.99	-11.0 mg/dL Standard Deviation 124.27
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 270	-27.3 mg/dL Standard Deviation 154.94	-17.5 mg/dL Standard Deviation 85.85
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	-37.2 mg/dL Standard Deviation 123.09	-17.9 mg/dL Standard Deviation 113.10

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in PCSK9 from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 90	9.1 Percentage change Interval -5.1 to 23.3	-53.5 Percentage change Interval -63.6 to -43.3
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 150	4.1 Percentage change Interval -14.3 to 22.6	-56.5 Percentage change Interval -69.9 to -43.1
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 180	39.2 Percentage change Interval 17.0 to 61.5	-53.1 Percentage change Interval -70.2 to -35.9

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Percentage Change in PCSK9 from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 270	-21.5 Percentage Change Standard Deviation 55.71	-14.4 Percentage Change Standard Deviation 160.60
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 330	-42.6 Percentage Change Standard Deviation 32.08	-57.0 Percentage Change Standard Deviation 30.36
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 450	-35.8 Percentage Change Standard Deviation 37.55	-51.1 Percentage Change Standard Deviation 27.90
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 510	-54.0 Percentage Change Standard Deviation 23.62	-59.4 Percentage Change Standard Deviation 24.13
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 630	-41.7 Percentage Change Standard Deviation 29.19	-48.1 Percentage Change Standard Deviation 32.65
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 690	-48.3 Percentage Change Standard Deviation 22.30	-64.3 Percentage Change Standard Deviation 11.21
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 720	-53.8 Percentage Change Standard Deviation 16.66	-57.6 Percentage Change Standard Deviation 39.76

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in PCSK9 from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 90	-25.8 ug/L Interval -110.3 to 58.6	-342.5 ug/L Interval -403.0 to -282.0
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 150	-30.7 ug/L Interval -114.4 to 52.9	-335.2 ug/L Interval -396.1 to -274.3
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 Day 180	88.8 ug/L Interval -1.2 to 178.9	-301.5 ug/L Interval -371.4 to -231.7

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Absolute Change in PCSK9 from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 720	-296.8 ug/L Standard Deviation 171.96	-413.2 ug/L Standard Deviation 460.33
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 270	-174.7 ug/L Standard Deviation 252.10	-234.4 ug/L Standard Deviation 242.25
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 330	-232.1 ug/L Standard Deviation 193.51	-392.0 ug/L Standard Deviation 422.93
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 450	-237.5 ug/L Standard Deviation 199.34	-387.6 ug/L Standard Deviation 483.81
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 510	-304.8 ug/L Standard Deviation 181.41	-381.0 ug/L Standard Deviation 261.04
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 630	-243.6 ug/L Standard Deviation 201.07	-303.1 ug/L Standard Deviation 200.37
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 Day 690	-275.5 ug/L Standard Deviation 163.85	-441.8 ug/L Standard Deviation 278.87

SECONDARY outcome

Timeframe: Baseline, Days 90, 150 and 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage change in total cholesterol from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 90	2.0 Percentage Change Interval -11.0 to 14.9	-5.9 Percentage Change Interval -15.1 to 3.3
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 150	-1.5 Percentage Change Interval -17.2 to 14.1	1.2 Percentage Change Interval -10.1 to 12.5
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 180	-1.4 Percentage Change Interval -13.8 to 11.0	-4.9 Percentage Change Interval -14.3 to 4.5

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in total cholesterol from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 90	3.9 mg/dL Interval -40.6 to 48.4	-15.1 mg/dL Interval -46.7 to 16.4
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 150	-10.5 mg/dL Interval -65.5 to 44.5	0.6 mg/dL Interval -39.2 to 40.4
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 Day 180	-6.8 mg/dL Interval -51.7 to 38.1	-12.6 mg/dL Interval -46.6 to 21.3

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Percentage change in total cholesterol from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 330	-10.9 Percentage Change Standard Deviation 27.67	-1.0 Percentage Change Standard Deviation 39.20
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 450	-4.2 Percentage Change Standard Deviation 22.45	-2.2 Percentage Change Standard Deviation 36.05
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 720	-11.2 Percentage Change Standard Deviation 21.86	-2.9 Percentage Change Standard Deviation 36.70
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 270	-7.4 Percentage Change Standard Deviation 34.80	-4.8 Percentage Change Standard Deviation 27.31
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 510	-6.4 Percentage Change Standard Deviation 25.37	2.8 Percentage Change Standard Deviation 46.77
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 630	-11.9 Percentage Change Standard Deviation 17.58	-4.8 Percentage Change Standard Deviation 33.84
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 690	-6.2 Percentage Change Standard Deviation 26.71	-1.9 Percentage Change Standard Deviation 33.83

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Absolute Change in total cholesterol from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 270	-24.9 mg/dL Standard Deviation 154.60	-13.3 mg/dL Standard Deviation 90.68
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 330	-35.6 mg/dL Standard Deviation 127.19	-13.0 mg/dL Standard Deviation 115.59
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 450	-7.9 mg/dL Standard Deviation 107.22	-14.4 mg/dL Standard Deviation 113.71
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 510	-17.8 mg/dL Standard Deviation 120.40	0.1 mg/dL Standard Deviation 128.73
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 630	-44.5 mg/dL Standard Deviation 71.81	-14.9 mg/dL Standard Deviation 111.50
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 690	-21.6 mg/dL Standard Deviation 118.21	-6.9 mg/dL Standard Deviation 114.58
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 Day 720	-40.4 mg/dL Standard Deviation 93.21	-8.5 mg/dL Standard Deviation 126.48

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population

Percentage change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180 demonstrated by Mixed Model Repeated Measures statisitical method.

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 90	6.3 Percentage change Interval -7.3 to 19.9	-6.4 Percentage change Interval -16.1 to 3.3
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 150	2.8 Percentage change Interval -12.5 to 18.1	-0.7 Percentage change Interval -11.8 to 10.3
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 180	4.5 Percentage change Interval -8.9 to 17.9	-5.8 Percentage change Interval -15.9 to 4.3

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Percentage Change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 270	-0.6 Percentage Change Standard Deviation 40.91	-3.3 Percentage Change Standard Deviation 28.67
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 330	-7.9 Percentage Change Standard Deviation 28.56	-3.6 Percentage Change Standard Deviation 34.35
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 450	-1.3 Percentage Change Standard Deviation 21.62	-3.5 Percentage Change Standard Deviation 35.66
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 510	-3.7 Percentage Change Standard Deviation 24.21	1.9 Percentage Change Standard Deviation 44.49
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 630	-7.3 Percentage Change Standard Deviation 17.81	-6.6 Percentage Change Standard Deviation 32.97
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 690	-3.7 Percentage Change Standard Deviation 27.16	-5.8 Percentage Change Standard Deviation 32.38
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 Day 720	-10.4 Percentage Change Standard Deviation 19.68	-8.0 Percentage Change Standard Deviation 31.93

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 90	10.0 mg/dL Interval -14.5 to 34.5	-9.4 mg/dL Interval -26.8 to 8.0
Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 150	3.3 mg/dL Interval -24.9 to 31.6	-1.4 mg/dL Interval -21.9 to 19.0
Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 Day 180	8.4 mg/dL Interval -16.5 to 33.3	-7.4 mg/dL Interval -26.2 to 11.4

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Absolute Change in Apolipoprotein B (Apo B) from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 510	-3.5 mg/dL Standard Deviation 58.45	1.1 mg/dL Standard Deviation 70.40
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 630	-15.4 mg/dL Standard Deviation 38.17	-10.1 mg/dL Standard Deviation 57.06
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 690	-10.6 mg/dL Standard Deviation 61.77	-10.3 mg/dL Standard Deviation 54.82
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 720	-22.1 mg/dL Standard Deviation 45.29	-13.0 mg/dL Standard Deviation 55.14
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 270	-1.3 mg/dL Standard Deviation 83.72	-1.9 mg/dL Standard Deviation 51.79
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 330	-11.5 mg/dL Standard Deviation 66.78	-7.3 mg/dL Standard Deviation 56.52
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 Day 450	3.0 mg/dL Standard Deviation 53.54	-6.9 mg/dL Standard Deviation 61.89

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage change in non-HDL-C levels from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	2.9 Percentage change Interval -12.4 to 18.2	-7.2 Percentage change Interval -18.1 to 3.6
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	-1.7 Percentage change Interval -19.9 to 16.6	1.3 Percentage change Interval -11.9 to 14.5
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-1.1 Percentage change Interval -15.6 to 13.3	-6.2 Percentage change Interval -17.1 to 4.7

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Percentage Change in non-HDL-C from Baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 270	-8.4 Percentage Change Standard Deviation 39.76	-7.6 Percentage Change Standard Deviation 30.95
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	-13.1 Percentage Change Standard Deviation 31.27	-2.3 Percentage Change Standard Deviation 45.56
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	-5.5 Percentage Change Standard Deviation 25.49	-3.1 Percentage Change Standard Deviation 43.73
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	-8.0 Percentage Change Standard Deviation 28.00	2.0 Percentage Change Standard Deviation 55.28
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-13.6 Percentage Change Standard Deviation 18.88	-6.5 Percentage Change Standard Deviation 40.16
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-6.4 Percentage Change Standard Deviation 30.12	-3.6 Percentage Change Standard Deviation 40.11
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-12.3 Percentage Change Standard Deviation 23.99	-5.0 Percentage Change Standard Deviation 43.40

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute change in non-HDL-C levels from Baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	3.8 mg/dL Interval -40.3 to 47.8	-15.3 mg/dL Interval -46.5 to 15.9
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	-11.6 mg/dL Interval -66.4 to 43.3	0.6 mg/dL Interval -39.1 to 40.3
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-5.7 mg/dL Interval -50.2 to 38.9	-12.7 mg/dL Interval -46.4 to 21.0

SECONDARY outcome

Timeframe: Baseline, Days 270, 330, 450, 510, 630, 690, and 720

Absolute Change in non-HDL Cholesterol (non-HDL-C) from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	-19.3 mg/dL Standard Deviation 120.58	-2.4 mg/dL Standard Deviation 128.45
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 270	-24.7 mg/dL Standard Deviation 157.98	-17.1 mg/dL Standard Deviation 86.34
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	-37.2 mg/dL Standard Deviation 127.12	-13.9 mg/dL Standard Deviation 114.51
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	-8.8 mg/dL Standard Deviation 109.91	-15.8 mg/dL Standard Deviation 112.63
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-43.8 mg/dL Standard Deviation 70.56	-14.7 mg/dL Standard Deviation 112.04
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-21.0 mg/dL Standard Deviation 116.12	-7.8 mg/dL Standard Deviation 114.44
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-38.9 mg/dL Standard Deviation 91.89	-9.3 mg/dL Standard Deviation 127.46

SECONDARY outcome

Timeframe: Days 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.

Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Individual Responsiveness of Subjects: Part 1 <25 mg/dL- Day 150	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 1 <50 mg/dL- Day 150	1 Participants	0 Participants
Individual Responsiveness of Subjects: Part 1 <70 mg/dL- Day 150	1 Participants	2 Participants
Individual Responsiveness of Subjects: Part 1 <100 mg/dL- Day 150	1 Participants	5 Participants
Individual Responsiveness of Subjects: Part 1 >= 100 mg/dL- Day 150	17 Participants	29 Participants
Individual Responsiveness of Subjects: Part 1 <25 mg/dL- Day 180	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 1 <50 mg/dL- Day 180	0 Participants	1 Participants
Individual Responsiveness of Subjects: Part 1 <70 mg/dL- Day 180	0 Participants	2 Participants
Individual Responsiveness of Subjects: Part 1 <100 mg/dL- Day 180	0 Participants	5 Participants
Individual Responsiveness of Subjects: Part 1 >= 100 mg/dL- Day 180	19 Participants	26 Participants

SECONDARY outcome

Timeframe: Days 330, 510, 690 and 720

Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Individual Responsiveness of Subjects: Part 2 >= 100 mg/dL- Day 510	16 Participants	25 Participants
Individual Responsiveness of Subjects: Part 2 <25 mg/dL- Day 690	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <100 mg/dL- Day 690	1 Participants	2 Participants
Individual Responsiveness of Subjects: Part 2 >= 100 mg/dL- Day 690	13 Participants	20 Participants
Individual Responsiveness of Subjects: Part 2 <25 mg/dL- Day 720	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <50 mg/dL- Day 720	0 Participants	1 Participants
Individual Responsiveness of Subjects: Part 2 <25 mg/dL- Day 330	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <50 mg/dL- Day 330	1 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <70 mg/dL- Day 330	2 Participants	1 Participants
Individual Responsiveness of Subjects: Part 2 <100 mg/dL- Day 330	2 Participants	5 Participants
Individual Responsiveness of Subjects: Part 2 >= 100 mg/dL- Day 330	14 Participants	20 Participants
Individual Responsiveness of Subjects: Part 2 <25 mg/dL- Day 510	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <50 mg/dL- Day 510	0 Participants	2 Participants
Individual Responsiveness of Subjects: Part 2 <70 mg/dL- Day 510	0 Participants	3 Participants
Individual Responsiveness of Subjects: Part 2 < 100 mg/dL- Day 510	1 Participants	5 Participants
Individual Responsiveness of Subjects: Part 2 <50 mg/dL- Day 690	0 Participants	0 Participants
Individual Responsiveness of Subjects: Part 2 <70 mg/dL- Day 690	0 Participants	1 Participants
Individual Responsiveness of Subjects: Part 2 <70 mg/dL- Day 720	1 Participants	1 Participants
Individual Responsiveness of Subjects: Part 2 <100 mg/dL- Day 720	1 Participants	5 Participants
Individual Responsiveness of Subjects: Part 2 >= 100 mg/dL- Day 720	17 Participants	22 Participants

SECONDARY outcome

Timeframe: Days 150, 180

Number of participants in each group who attain global lipid targets for their indication

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Proportional Responsiveness: Part 1 Day 150	1 Participants	3 Participants
Proportional Responsiveness: Part 1 Day 180	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Days 330, 510, 690 and 720

Number of participants in each group who attain global lipid targets for their indication

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Proportional Responsiveness of Subjects: Part 2 Day 330	2 Participants	2 Participants
Proportional Responsiveness of Subjects: Part 2 Day 510	0 Participants	4 Participants
Proportional Responsiveness of Subjects: Part 2 Day 690	0 Participants	1 Participants
Proportional Responsiveness of Subjects: Part 2 Day 720	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 1 (Days 90, 150, 180)

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=20%: Day 90	4 Participants	14 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=20%: Day 150	3 Participants	9 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=20%: Day 180	3 Participants	12 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=30%: Day 90	3 Participants	13 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=30%: Day 150	3 Participants	6 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 LDL-C >=30%: Day 180	2 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Days 330, 510, 690, and 720

Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 2 (Days 330, 510, 690, and 720)

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=20%: Day 330	5 Participants	13 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=20%: Day 510	6 Participants	11 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=20%: Day 690	8 Participants	11 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=20%: Day 720	7 Participants	13 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=30%: Day 330	4 Participants	8 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=30%: Day 510	4 Participants	9 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=30%: Day 690	4 Participants	5 Participants
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 LDL-C >=30%: Day 720	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	-1.1 Percentage change Interval -8.6 to 6.5	1.4 Percentage change Interval -4.0 to 6.7
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	2.3 Percentage change Interval -8.0 to 12.6	3.6 Percentage change Interval -3.9 to 11.1
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-1.9 Percentage change Interval -9.8 to 6.0	1.5 Percentage change Interval -4.5 to 7.6

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Percentage change in LDL-C levels from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	3.2 Percentage change Standard Deviation 13.09	4.3 Percentage change Standard Deviation 16.45
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	1.6 Percentage change Standard Deviation 12.26	4.8 Percentage change Standard Deviation 17.81
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	2.9 Percentage change Standard Deviation 19.83	7.9 Percentage change Standard Deviation 17.75
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-2.0 Percentage change Standard Deviation 14.81	0.5 Percentage change Standard Deviation 15.81
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-2.4 Percentage change Standard Deviation 19.17	4.5 Percentage change Standard Deviation 20.31
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-3.6 Percentage change Standard Deviation 14.90	4.1 Percentage change Standard Deviation 16.99

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	-0.0 mg/dL Interval -3.4 to 3.4	0.2 mg/dL Interval -2.2 to 2.6
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	1.0 mg/dL Interval -3.5 to 5.4	-0.0 mg/dL Interval -3.2 to 3.2
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	-1.2 mg/dL Interval -4.5 to 2.1	0.0 mg/dL Interval -2.5 to 2.5

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	1.6 mg/dL Standard Deviation 6.05	0.9 mg/dL Standard Deviation 6.85
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	0.9 mg/dL Standard Deviation 6.04	1.4 mg/dL Standard Deviation 8.53
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	1.5 mg/dL Standard Deviation 8.78	2.5 mg/dL Standard Deviation 7.86
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	-0.7 mg/dL Standard Deviation 7.35	-0.2 mg/dL Standard Deviation 7.70
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	-0.6 mg/dL Standard Deviation 9.57	1.0 mg/dL Standard Deviation 8.31
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	-1.5 mg/dL Standard Deviation 7.22	0.8 mg/dL Standard Deviation 7.34

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in VLDL-C levels from baseline to subsequent visits on Days 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	0.6 mg/dL Interval -2.8 to 4.0	1.6 mg/dL Interval -0.9 to 4.0
Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	3.0 mg/dL Interval -1.3 to 7.3	0.4 mg/dL Interval -2.7 to 3.4
Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	1.8 mg/dL Interval -3.0 to 6.5	1.5 mg/dL Interval -2.1 to 5.1

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Absolute change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	0.0 mg/dL Standard Deviation 9.38	2.7 mg/dL Standard Deviation 8.03
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	1.1 mg/dL Standard Deviation 5.84	4.4 mg/dL Standard Deviation 8.91
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	-0.9 mg/dL Standard Deviation 4.76	-0.2 mg/dL Standard Deviation 8.85
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	6.7 mg/dL Standard Deviation 13.76	0.2 mg/dL Standard Deviation 8.39
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	6.9 mg/dL Standard Deviation 14.58	0.8 mg/dL Standard Deviation 9.34
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	2.5 mg/dL Standard Deviation 6.81	1.7 mg/dL Standard Deviation 9.06

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in VLDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 90	0.6 Percentage change Interval -17.4 to 18.7	11.9 Percentage change Interval -1.0 to 24.9
Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 150	16.3 Percentage change Interval -1.6 to 34.1	4.9 Percentage change Interval -7.8 to 17.6
Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 Day 180	10.0 Percentage change Interval -13.4 to 33.5	12.3 Percentage change Interval -5.3 to 29.9

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Percentage change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 330	6.8 Percentage Change Standard Deviation 38.92	20.8 Percentage Change Standard Deviation 57.44
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 450	7.1 Percentage Change Standard Deviation 28.86	23.9 Percentage Change Standard Deviation 46.36
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 510	2.1 Percentage Change Standard Deviation 33.45	7.1 Percentage Change Standard Deviation 43.16
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 630	25.1 Percentage Change Standard Deviation 44.22	6.2 Percentage Change Standard Deviation 46.21
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 690	26.5 Percentage Change Standard Deviation 51.79	11.4 Percentage Change Standard Deviation 59.86
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 Day 720	13.9 Percentage Change Standard Deviation 33.26	12.4 Percentage Change Standard Deviation 50.37

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Days 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 Day 90	2.6 mg/dL Interval -5.2 to 10.3	0.6 mg/dL Interval -4.9 to 6.1
Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 Day 150	4.0 mg/dL Interval -6.5 to 14.6	-1.4 mg/dL Interval -9.1 to 6.3
Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 Day 180	1.4 mg/dL Interval -6.9 to 9.8	-1.3 mg/dL Interval -7.7 to 5.1

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Absolute change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 330	0.9 mg/dL Standard Deviation 14.14	1.2 mg/dL Standard Deviation 13.85
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 450	4.9 mg/dL Standard Deviation 14.04	4.7 mg/dL Standard Deviation 16.59
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 510	6.7 mg/dL Standard Deviation 20.39	7.8 mg/dL Standard Deviation 16.32
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 630	5.4 mg/dL Standard Deviation 15.59	1.3 mg/dL Standard Deviation 13.11
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 690	6.9 mg/dL Standard Deviation 17.07	9.3 mg/dL Standard Deviation 15.69
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 720	3.9 mg/dL Standard Deviation 15.15	6.9 mg/dL Standard Deviation 11.30

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Day 90, 150, and 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 Day 90	1.6 Percentage change Interval -4.5 to 7.6	0.6 Percentage change Interval -3.7 to 4.9
Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 Day 150	3.0 Percentage change Interval -5.1 to 11.1	0.4 Percentage change Interval -5.5 to 6.3
Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 Day 180	1.6 Percentage change Interval -5.0 to 8.3	-1.0 Percentage change Interval -6.1 to 4.1

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Percentage change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 330	0.4 Percentage change Standard Deviation 11.37	1.3 Percentage change Standard Deviation 10.80
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 450	4.4 Percentage change Standard Deviation 10.76	3.9 Percentage change Standard Deviation 12.71
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 510	6.2 Percentage change Standard Deviation 17.00	6.8 Percentage change Standard Deviation 13.40
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 630	5.4 Percentage change Standard Deviation 11.11	0.8 Percentage change Standard Deviation 9.93
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 690	5.6 Percentage change Standard Deviation 13.92	7.2 Percentage change Standard Deviation 12.17
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 Day 720	3.5 Percentage change Standard Deviation 11.71	5.5 Percentage change Standard Deviation 9.27

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in Lp(a) from Baseline to Subsequent Visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 90	4.3 Percentage change Interval -6.2 to 14.7	-4.6 Percentage change Interval -12.2 to 2.9
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 150	15.2 Percentage change Interval -6.8 to 37.2	-3.8 Percentage change Interval -19.8 to 12.2
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 180	4.9 Percentage change Interval -6.5 to 16.4	-4.8 Percentage change Interval -13.5 to 4.0

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Percentage change in Lp(a) from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 630	-8.4 Percentage change Standard Deviation 32.65	1.7 Percentage change Standard Deviation 29.43
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 690	-10.7 Percentage change Standard Deviation 34.02	-5.3 Percentage change Standard Deviation 27.44
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 720	-11.4 Percentage change Standard Deviation 51.06	-3.1 Percentage change Standard Deviation 45.08
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 330	2.5 Percentage change Standard Deviation 33.15	-1.4 Percentage change Standard Deviation 26.69
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 450	3.4 Percentage change Standard Deviation 45.12	0.2 Percentage change Standard Deviation 26.42
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 510	8.3 Percentage change Standard Deviation 44.74	13.4 Percentage change Standard Deviation 39.37

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Absolute Change in Lp(a) from baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 90	5.8 nmol/L Interval -9.4 to 20.9	-3.8 nmol/L Interval -14.7 to 7.1
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 150	3.9 nmol/L Interval -12.8 to 20.6	-5.6 nmol/L Interval -17.7 to 6.5
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 Day 180	1.2 nmol/L Interval -12.4 to 14.7	-5.1 nmol/L Interval -15.3 to 5.2

SECONDARY outcome

Timeframe: Baseline, Days 330, 450, 510, 630, 690, and 720

Absolute change in Lp(a) from Baseline to Subsequent Visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 330	-3.1 nmol/L Standard Deviation 36.71	-5.2 nmol/L Standard Deviation 30.65
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 450	-3.8 nmol/L Standard Deviation 47.48	3.1 nmol/L Standard Deviation 41.28
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 510	14.5 nmol/L Standard Deviation 50.25	18.4 nmol/L Standard Deviation 53.31
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 630	-2.4 nmol/L Standard Deviation 31.18	13.7 nmol/L Standard Deviation 50.77
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 690	-5.3 nmol/L Standard Deviation 26.52	5.8 nmol/L Standard Deviation 26.46
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 Day 720	-6.0 nmol/L Standard Deviation 48.12	5.2 nmol/L Standard Deviation 30.44

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Population: ITT Population (Part 1): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.

Percent change in hsCRP from Baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 90	41.2 Percentage Change Standard Deviation 243.94	42.0 Percentage Change Standard Deviation 170.41
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 150	230.8 Percentage Change Standard Deviation 640.11	126.9 Percentage Change Standard Deviation 380.15
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 180	115.1 Percentage Change Standard Deviation 490.17	45.2 Percentage Change Standard Deviation 143.24

SECONDARY outcome

Timeframe: Baseline, Days 330, 510 ,690, 720

Percentage change in hsCRP from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 690	29.0 Percentage Change Standard Deviation 125.18	37.5 Percentage Change Standard Deviation 92.40
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 330	178.9 Percentage Change Standard Deviation 657.67	17.3 Percentage Change Standard Deviation 73.29
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 510	266.7 Percentage Change Standard Deviation 936.76	64.7 Percentage Change Standard Deviation 204.54
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 720	49.6 Percentage Change Standard Deviation 167.16	38.60 Percentage Change Standard Deviation 112.57

SECONDARY outcome

Timeframe: Baseline, Days 90, 150, 180

Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from Baseline to subsequent visits up to Day 180

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 90	-3.2 mg/L Standard Deviation 9.46	0.7 mg/L Standard Deviation 4.25
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 150	0.5 mg/L Standard Deviation 15.07	1.1 mg/L Standard Deviation 6.51
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 Day 180	-3.8 mg/L Standard Deviation 9.33	0.2 mg/L Standard Deviation 3.75

SECONDARY outcome

Timeframe: Baseline, Days 330, 510, 690, 720

Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from baseline to subsequent visits up to Day 720

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 330	-4.0 mg/L Standard Deviation 9.98	-0.4 mg/L Standard Deviation 2.81
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 510	-3.4 mg/L Standard Deviation 10.07	0.9 mg/L Standard Deviation 4.75
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 690	-4.7 mg/L Standard Deviation 10.21	0.7 mg/L Standard Deviation 3.94
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 Day 720	-3.7 mg/L Standard Deviation 9.86	-0.2 mg/L Standard Deviation 4.25

SECONDARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage change in Apo-B from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Apo-B From Baseline to Day 150	3.55 Percentage change Interval -13.6 to 20.71	-0.75 Percentage change Interval -11.5 to 9.99

SECONDARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage Change in non-HDL-C from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Non-HDL-C From Baseline to Day 150	2.46 Percentage Change Interval -19.12 to 24.05	0.37 Percentage Change Interval -12.68 to 13.42

SECONDARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Percentage change in total cholesterol from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=19 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=37 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Percent Change in Total Cholesterol From Baseline to Day 150	1.51 Percentage Change Interval -16.49 to 19.5	0.71 Percentage Change Interval -10.39 to 11.82

SECONDARY outcome

Timeframe: Baseline, Day 150

Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.

Number of participants in each group with ≥30% LDL-C reduction from baseline at Day 150 using the Regression Logistic Statistical Model

Outcome measures

Outcome measures
Measure	Part 1 - Placebo n=18 Participants Participants who received a dose of placebos administered by SC injection on Day 1 and Day 90.	Part 1 - Inclisiran n=34 Participants Participants who received a dose of 300 milligram (mg) inclisiran sodium for injection administered by SC injection on Day 1 and Day 90.
Proportion of Subjects With ≥30% LDL-C Reduction of From Baseline at Day 150	3 Participants	6 Participants

Adverse Events

Part 1: Inclisiran

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Part 1: Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1:All Patients

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Part 2: Inclisiran

Serious events: 11 serious events

Other events: 29 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER