Familial Hypercholesterolemia - Heterozygous
Conditions
Keywords
Heterozygous familial hypercholesterolemia (HeFH), LDL-cholesterol (LDL-C), adolescents, pediatric, small interfering ribonucleic acid (siRNA)
Brief summary
This was a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C).
Detailed description
This was a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective was to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.
Interventions
DRUGInclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection
DRUGPlacebo
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masked (Year 1) to No Masking (Year 2)
Intervention model description
Parallel (Year 1) to single-group (Year 2)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria * Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening * Fasting triglycerides \<400 mg/dL (4.5 mmol/L) at screening * On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
Exclusion criteria
* Homozygous familial hypercholesterolemia (HoFH) * Active liver disease * Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome * Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening) * Recent and/or planned use of other investigational medicinal products or devices
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) | Baseline and Day 330 | Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1) | Baseline and Day 330 | Absolute change in LDL-C from baseline to Day 330. |
| Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1) | Baseline and Day 330 | Percentage change in apolipoprotein B (Apo B) from baseline to Day 330. |
| Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1) | Baseline and Day 330 | Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to Day 330. |
| Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1) | Baseline and Day 330 | Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to Day 330. |
| Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1) | Baseline and Day 330 | Percentage change in total cholesterol from baseline to Day 330. |
| Percent Change in LDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in LDL-C from baseline to each assessment time up to Day 720. |
| Absolute Change in LDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in LDL-C from baseline to each assessment time up to Day 720. |
| Percent Change in Apo B From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720. |
| Absolute Change in Apo B From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720. |
| Percent Change in Lp(a) From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720. |
| Absolute Change in Lp(a) From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720. |
| Percent Change in Non-HDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720. |
| Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1) | Baseline, after Day 90 up to Day 330 | Time-adjusted percent change in LDL-C (after Day 90 and up to Day 330), calculated as the average of percent changes from baseline to Days 150, 270 and 330 |
| Percent Change in Total Cholesterol From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in total cholesterol from baseline to each assessment time up to Day 720. |
| Absolute Change in Total Cholesterol From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in total cholesterol from baseline to each assessment time up to Day 720. |
| Percent Change in Triglycerides From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in triglycerides from baseline to each assessment time up to Day 720. |
| Absolute Change in Triglycerides From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in triglycerides from baseline to each assessment time up to Day 720. |
| Percent Change in HDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720. |
| Absolute Change in HDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720. |
| Percent Change in VLDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720. |
| Absolut Change in VLDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720. |
| Percent Change in Apo A1 From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720. |
| Absolute Change in Apo A1 From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720. |
| Percent Change in PCSK9 From Baseline up to Day 720 | Baseline, up to Day 720 | Percentage change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720. |
| Absolut Change in PCSK9 From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720. |
| Absolute Change in Non-HDL-C From Baseline up to Day 720 | Baseline, up to Day 720 | Absolute change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720. |
Countries
Argentina, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Jordan, Lebanon, Malaysia, Netherlands, Norway, Poland, Russia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
141 participants were randomized in 26 countries and 51 study centers:Argentina (1), Brazil (3), Canada (1), Czech Republic (2), France (3), Germany (2), Greece (1), Hungary (1), Israel (2), Italy (4), Jordan (1), Lebanon (1), Malaysia (1), Netherlands (2), Norway (1), Poland (2), Russian Federation (2), Slovakia (1), Slovenia (1), South Africa (3), Spain (4), Switzerland (1), Taiwan (1), Turkey (4), United Kingdom (1), and United States of America (5).
Pre-assignment details
The study had an approximately 4-week screening/run-in period
Participants by arm
| Arm | Count |
|---|---|
| Part 1- Inclisiran Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270) | 93 |
| Part 1 - Placebo Placebo sc injection (given at Day 1, 90 and 270) | 48 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1 (Double-blind Period) | Participant/guardian decision | 1 | 0 | 0 |
| Part 1 (Double-blind Period) | Physician Decision | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1- Inclisiran | Part 1 - Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 93 Participants | 48 Participants | 141 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.2 years STANDARD_DEVIATION 2.02 | 14.9 years STANDARD_DEVIATION 1.8 | 15.1 years STANDARD_DEVIATION 1.94 |
| Race/Ethnicity, Customized Asian | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 80 Participants | 48 Participants | 128 Participants |
| Sex: Female, Male Female | 51 Participants | 24 Participants | 75 Participants |
| Sex: Female, Male Male | 42 Participants | 24 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 48 | 0 / 139 |
| other Total, other adverse events | 57 / 93 | 29 / 48 | 52 / 139 |
| serious Total, serious adverse events | 3 / 93 | 1 / 48 | 6 / 139 |
Outcome results
Primary
Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)
Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) | -27.14 percent change in LDL-C |
| Part 1 - Placebo | Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1) | 1.40 percent change in LDL-C |
p-value: <0.000195% CI: [-35.81, -21.27]ANCOVA
Secondary
Absolut Change in PCSK9 From Baseline up to Day 720
Absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 150 | -274.8 ng/mL | Standard Deviation 116.2 |
| Part 1- Inclisiran | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 330 | -278.2 ng/mL | Standard Deviation 119.8 |
| Part 1- Inclisiran | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 90 | -259.6 ng/mL | Standard Deviation 121.5 |
| Part 1- Inclisiran | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 360 | -275.4 ng/mL | Standard Deviation 117.2 |
| Part 1 - Placebo | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 150 | -27.7 ng/mL | Standard Deviation 210.44 |
| Part 1 - Placebo | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 90 | 2.1 ng/mL | Standard Deviation 223.16 |
| Part 1 - Placebo | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 330 | -23.9 ng/mL | Standard Deviation 210.85 |
| Part 1 - Placebo | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 360 | -9.1 ng/mL | Standard Deviation 245.36 |
| Part 2 - Inclisiran (Total) | Absolut Change in PCSK9 From Baseline up to Day 720 | DAY 510 | -288.1 ng/mL | Standard Deviation 156.9 |
| Part 2 - Inclisiran (Total) | Absolut Change in PCSK9 From Baseline up to Day 720 | Day 720 (study completion) | -279.5 ng/mL | Standard Deviation 159.2 |
Secondary
Absolut Change in VLDL-C From Baseline up to Day 720
Absolute change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 150 | 0.7 mg/dL | Standard Deviation 10.02 |
| Part 1- Inclisiran | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 330 | -0.7 mg/dL | Standard Deviation 7.04 |
| Part 1- Inclisiran | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 360 | -0.7 mg/dL | Standard Deviation 7.63 |
| Part 1 - Placebo | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 330 | 0.8 mg/dL | Standard Deviation 7.07 |
| Part 1 - Placebo | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 150 | -0.9 mg/dL | Standard Deviation 6.37 |
| Part 1 - Placebo | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 360 | -0.2 mg/dL | Standard Deviation 5.66 |
| Part 2 - Inclisiran (Total) | Absolut Change in VLDL-C From Baseline up to Day 720 | DAY 510 | -1.2 mg/dL | Standard Deviation 6.9 |
| Part 2 - Inclisiran (Total) | Absolut Change in VLDL-C From Baseline up to Day 720 | Day 720 (study completion) | -1.0 mg/dL | Standard Deviation 7.4 |
Secondary
Absolute Change in Apo A1 From Baseline up to Day 720
Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 150 | 3.3 mg/dL | Standard Deviation 21.76 |
| Part 1- Inclisiran | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 330 | 6.1 mg/dL | Standard Deviation 21.16 |
| Part 1- Inclisiran | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 360 | 2.7 mg/dL | Standard Deviation 21.87 |
| Part 1 - Placebo | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 360 | -2.6 mg/dL | Standard Deviation 13.89 |
| Part 1 - Placebo | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 150 | 0.0 mg/dL | Standard Deviation 17.72 |
| Part 1 - Placebo | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 330 | -2.8 mg/dL | Standard Deviation 14.24 |
| Part 2 - Inclisiran (Total) | Absolute Change in Apo A1 From Baseline up to Day 720 | DAY 510 | 7.5 mg/dL | Standard Deviation 22.24 |
| Part 2 - Inclisiran (Total) | Absolute Change in Apo A1 From Baseline up to Day 720 | Day 720 (study completion) | 5.4 mg/dL | Standard Deviation 21.61 |
Secondary
Absolute Change in Apo B From Baseline up to Day 720
Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Apo B From Baseline up to Day 720 | DAY 150 | -33.3 mg/dL | Standard Deviation 28.2 |
| Part 1- Inclisiran | Absolute Change in Apo B From Baseline up to Day 720 | DAY 360 | -26.1 mg/dL | Standard Deviation 29.59 |
| Part 1- Inclisiran | Absolute Change in Apo B From Baseline up to Day 720 | DAY 330 | -29.2 mg/dL | Standard Deviation 28.04 |
| Part 1 - Placebo | Absolute Change in Apo B From Baseline up to Day 720 | DAY 360 | -0.6 mg/dL | Standard Deviation 28.72 |
| Part 1 - Placebo | Absolute Change in Apo B From Baseline up to Day 720 | DAY 330 | 2.9 mg/dL | Standard Deviation 23.47 |
| Part 1 - Placebo | Absolute Change in Apo B From Baseline up to Day 720 | DAY 150 | 0.0 mg/dL | Standard Deviation 27.38 |
| Part 2 - Inclisiran (Total) | Absolute Change in Apo B From Baseline up to Day 720 | Day 720 (study completion) | -35.4 mg/dL | Standard Deviation 33.83 |
| Part 2 - Inclisiran (Total) | Absolute Change in Apo B From Baseline up to Day 720 | DAY 510 | -33.5 mg/dL | Standard Deviation 32.13 |
Secondary
Absolute Change in HDL-C From Baseline up to Day 720
Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 330 | 3.2 mg/dL | Standard Deviation 9.57 |
| Part 1- Inclisiran | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 360 | 1.5 mg/dL | Standard Deviation 9.59 |
| Part 1- Inclisiran | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 150 | 1.2 mg/dL | Standard Deviation 10.23 |
| Part 1 - Placebo | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 150 | 0.9 mg/dL | Standard Deviation 8.07 |
| Part 1 - Placebo | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 330 | -1.4 mg/dL | Standard Deviation 7.77 |
| Part 1 - Placebo | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 360 | -0.1 mg/dL | Standard Deviation 6.23 |
| Part 2 - Inclisiran (Total) | Absolute Change in HDL-C From Baseline up to Day 720 | DAY 510 | 2.4 mg/dL | Standard Deviation 9.32 |
| Part 2 - Inclisiran (Total) | Absolute Change in HDL-C From Baseline up to Day 720 | Day 720 (study completion) | 2.8 mg/dL | Standard Deviation 9.75 |
Secondary
Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)
Absolute change in LDL-C from baseline to Day 330.
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1) | -50.54 mg/dL |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1) | -0.55 mg/dL |
p-value: <0.000195% CI: [-63.18, -36.81]ANCOVA
Secondary
Absolute Change in LDL-C From Baseline up to Day 720
Absolute change in LDL-C from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 90 | -45.4 mg/dL | Standard Deviation 45.26 |
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 330 | -51.9 mg/dL | Standard Deviation 45.47 |
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 150 | -61.0 mg/dL | Standard Deviation 45.84 |
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 360 | -49.0 mg/dL | Standard Deviation 44.49 |
| Part 1- Inclisiran | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 270 | -38.4 mg/dL | Standard Deviation 55.77 |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 330 | -0.3 mg/dL | Standard Deviation 38.04 |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 150 | 6.6 mg/dL | Standard Deviation 46.22 |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 90 | -3.0 mg/dL | Standard Deviation 35.02 |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 270 | 1.0 mg/dL | Standard Deviation 36.92 |
| Part 1 - Placebo | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 360 | -2.9 mg/dL | Standard Deviation 51.74 |
| Part 2 - Inclisiran (Total) | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 450 | -46.3 mg/dL | Standard Deviation 52.51 |
| Part 2 - Inclisiran (Total) | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 510 | -60.8 mg/dL | Standard Deviation 48.88 |
| Part 2 - Inclisiran (Total) | Absolute Change in LDL-C From Baseline up to Day 720 | DAY 630 | -50.9 mg/dL | Standard Deviation 50.3 |
| Part 2 - Inclisiran (Total) | Absolute Change in LDL-C From Baseline up to Day 720 | Day 720 (study completion) | -64.1 mg/dL | Standard Deviation 53.91 |
Secondary
Absolute Change in Lp(a) From Baseline up to Day 720
Absolute change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 150 | -12.5 nmol/L | Standard Deviation 34.73 |
| Part 1- Inclisiran | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 360 | -10.2 nmol/L | Standard Deviation 31.16 |
| Part 1- Inclisiran | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 330 | -9.5 nmol/L | Standard Deviation 33.81 |
| Part 1 - Placebo | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 150 | 3.2 nmol/L | Standard Deviation 20.67 |
| Part 1 - Placebo | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 330 | 5.3 nmol/L | Standard Deviation 21.55 |
| Part 1 - Placebo | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 360 | 4.4 nmol/L | Standard Deviation 22.99 |
| Part 2 - Inclisiran (Total) | Absolute Change in Lp(a) From Baseline up to Day 720 | Day 720 (study completion) | -9.0 nmol/L | Standard Deviation 50.08 |
| Part 2 - Inclisiran (Total) | Absolute Change in Lp(a) From Baseline up to Day 720 | DAY 510 | -10.1 nmol/L | Standard Deviation 34.98 |
Secondary
Absolute Change in Non-HDL-C From Baseline up to Day 720
Absolute change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 360 | -49.7 mg/dL | Standard Deviation 46.3 |
| Part 1- Inclisiran | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 330 | -52.6 mg/dL | Standard Deviation 46.93 |
| Part 1- Inclisiran | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 150 | -60.2 mg/dL | Standard Deviation 47.41 |
| Part 1 - Placebo | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 150 | 5.7 mg/dL | Standard Deviation 47.61 |
| Part 1 - Placebo | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 330 | 0.5 mg/dL | Standard Deviation 39.2 |
| Part 1 - Placebo | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 360 | -3.0 mg/dL | Standard Deviation 52.75 |
| Part 2 - Inclisiran (Total) | Absolute Change in Non-HDL-C From Baseline up to Day 720 | Day 720 (study completion) | -65.1 mg/dL | Standard Deviation 56.16 |
| Part 2 - Inclisiran (Total) | Absolute Change in Non-HDL-C From Baseline up to Day 720 | DAY 510 | -62.0 mg/dL | Standard Deviation 51.09 |
Secondary
Absolute Change in Total Cholesterol From Baseline up to Day 720
Absolute change in total cholesterol from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 330 | -49.4 mg/dL | Standard Deviation 47.77 |
| Part 1- Inclisiran | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 150 | -59.0 mg/dL | Standard Deviation 47.79 |
| Part 1- Inclisiran | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 360 | -48.2 mg/dL | Standard Deviation 47.06 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 360 | -3.1 mg/dL | Standard Deviation 52.66 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 150 | 6.6 mg/dL | Standard Deviation 48.08 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 330 | -0.9 mg/dL | Standard Deviation 38.48 |
| Part 2 - Inclisiran (Total) | Absolute Change in Total Cholesterol From Baseline up to Day 720 | Day 720 (study completion) | -62.3 mg/dL | Standard Deviation 55.05 |
| Part 2 - Inclisiran (Total) | Absolute Change in Total Cholesterol From Baseline up to Day 720 | DAY 510 | -59.6 mg/dL | Standard Deviation 51.06 |
Secondary
Absolute Change in Triglycerides From Baseline up to Day 720
Absolute change in triglycerides from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 330 | -2.9 mg/dL | Standard Deviation 35.01 |
| Part 1- Inclisiran | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 150 | 6.9 mg/dL | Standard Deviation 64.67 |
| Part 1- Inclisiran | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 360 | -3.1 mg/dL | Standard Deviation 38.13 |
| Part 1 - Placebo | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 360 | -1.7 mg/dL | Standard Deviation 28.47 |
| Part 1 - Placebo | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 150 | -4.8 mg/dL | Standard Deviation 31.53 |
| Part 1 - Placebo | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 330 | 3.5 mg/dL | Standard Deviation 35.55 |
| Part 2 - Inclisiran (Total) | Absolute Change in Triglycerides From Baseline up to Day 720 | Day 720 (study completion) | -4.8 mg/dL | Standard Deviation 36.21 |
| Part 2 - Inclisiran (Total) | Absolute Change in Triglycerides From Baseline up to Day 720 | DAY 510 | -4.2 mg/dL | Standard Deviation 34.7 |
Secondary
Percent Change in Apo A1 From Baseline up to Day 720
Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 150 | 3.7 Percent change in Apo A1 | Standard Deviation 15.4 |
| Part 1- Inclisiran | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 330 | 5.2 Percent change in Apo A1 | Standard Deviation 14.49 |
| Part 1- Inclisiran | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 360 | 3.0 Percent change in Apo A1 | Standard Deviation 15.12 |
| Part 1 - Placebo | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 330 | -1.5 Percent change in Apo A1 | Standard Deviation 10.58 |
| Part 1 - Placebo | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 150 | 0.4 Percent change in Apo A1 | Standard Deviation 13.22 |
| Part 1 - Placebo | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 360 | -1.5 Percent change in Apo A1 | Standard Deviation 9.98 |
| Part 2 - Inclisiran (Total) | Percent Change in Apo A1 From Baseline up to Day 720 | DAY 510 | 6.3 Percent change in Apo A1 | Standard Deviation 16.19 |
| Part 2 - Inclisiran (Total) | Percent Change in Apo A1 From Baseline up to Day 720 | Day 720 (study completion) | 4.9 Percent change in Apo A1 | Standard Deviation 15.56 |
Secondary
Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)
Percentage change in apolipoprotein B (Apo B) from baseline to Day 330.
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1) | -21.46 Percent change in Apo B |
| Part 1 - Placebo | Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1) | 4.24 Percent change in Apo B |
p-value: <0.000195% CI: [-31.68, -19.73]ANCOVA
Secondary
Percent Change in Apo B From Baseline up to Day 720
Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Apo B From Baseline up to Day 720 | DAY 150 | -25.1 Percent change in Apo B | Standard Deviation 18.18 |
| Part 1- Inclisiran | Percent Change in Apo B From Baseline up to Day 720 | DAY 330 | -21.9 Percent change in Apo B | Standard Deviation 19.51 |
| Part 1- Inclisiran | Percent Change in Apo B From Baseline up to Day 720 | DAY 360 | -19.3 Percent change in Apo B | Standard Deviation 21.36 |
| Part 1 - Placebo | Percent Change in Apo B From Baseline up to Day 720 | DAY 330 | 3.9 Percent change in Apo B | Standard Deviation 18.13 |
| Part 1 - Placebo | Percent Change in Apo B From Baseline up to Day 720 | DAY 360 | 1.7 Percent change in Apo B | Standard Deviation 22.7 |
| Part 1 - Placebo | Percent Change in Apo B From Baseline up to Day 720 | DAY 150 | 2.2 Percent change in Apo B | Standard Deviation 20.77 |
| Part 2 - Inclisiran (Total) | Percent Change in Apo B From Baseline up to Day 720 | Day 720 (study completion) | -25.7 Percent change in Apo B | Standard Deviation 21.71 |
| Part 2 - Inclisiran (Total) | Percent Change in Apo B From Baseline up to Day 720 | DAY 510 | -24.5 Percent change in Apo B | Standard Deviation 21.77 |
Secondary
Percent Change in HDL-C From Baseline up to Day 720
Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in HDL-C From Baseline up to Day 720 | DAY 150 | 3.6 Percent change in HDL-C | Standard Deviation 18.88 |
| Part 1- Inclisiran | Percent Change in HDL-C From Baseline up to Day 720 | DAY 360 | 4.4 Percent change in HDL-C | Standard Deviation 19.54 |
| Part 1- Inclisiran | Percent Change in HDL-C From Baseline up to Day 720 | DAY 330 | 7.4 Percent change in HDL-C | Standard Deviation 19.15 |
| Part 1 - Placebo | Percent Change in HDL-C From Baseline up to Day 720 | DAY 150 | 3.6 Percent change in HDL-C | Standard Deviation 16.49 |
| Part 1 - Placebo | Percent Change in HDL-C From Baseline up to Day 720 | DAY 360 | 0.9 Percent change in HDL-C | Standard Deviation 12.39 |
| Part 1 - Placebo | Percent Change in HDL-C From Baseline up to Day 720 | DAY 330 | -1.9 Percent change in HDL-C | Standard Deviation 16.15 |
| Part 2 - Inclisiran (Total) | Percent Change in HDL-C From Baseline up to Day 720 | DAY 510 | 6.6 Percent change in HDL-C | Standard Deviation 19.84 |
| Part 2 - Inclisiran (Total) | Percent Change in HDL-C From Baseline up to Day 720 | Day 720 (study completion) | 7.4 Percent change in HDL-C | Standard Deviation 20.4 |
Secondary
Percent Change in LDL-C From Baseline up to Day 720
Percentage change in LDL-C from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in LDL-C From Baseline up to Day 720 | DAY 330 | -27.8 Percent change in LDL-C | Standard Deviation 22.95 |
| Part 1- Inclisiran | Percent Change in LDL-C From Baseline up to Day 720 | DAY 90 | -23.9 Percent change in LDL-C | Standard Deviation 22.14 |
| Part 1- Inclisiran | Percent Change in LDL-C From Baseline up to Day 720 | DAY 150 | -32.5 Percent change in LDL-C | Standard Deviation 21.47 |
| Part 1- Inclisiran | Percent Change in LDL-C From Baseline up to Day 720 | DAY 270 | -19.0 Percent change in LDL-C | Standard Deviation 28.31 |
| Part 1- Inclisiran | Percent Change in LDL-C From Baseline up to Day 720 | DAY 360 | -26.1 Percent change in LDL-C | Standard Deviation 22.71 |
| Part 1 - Placebo | Percent Change in LDL-C From Baseline up to Day 720 | DAY 270 | 2.1 Percent change in LDL-C | Standard Deviation 22.44 |
| Part 1 - Placebo | Percent Change in LDL-C From Baseline up to Day 720 | DAY 90 | -0.1 Percent change in LDL-C | Standard Deviation 20.16 |
| Part 1 - Placebo | Percent Change in LDL-C From Baseline up to Day 720 | DAY 360 | 1.5 Percent change in LDL-C | Standard Deviation 30.56 |
| Part 1 - Placebo | Percent Change in LDL-C From Baseline up to Day 720 | DAY 150 | 6.4 Percent change in LDL-C | Standard Deviation 28.83 |
| Part 1 - Placebo | Percent Change in LDL-C From Baseline up to Day 720 | DAY 330 | 1.5 Percent change in LDL-C | Standard Deviation 20.59 |
| Part 2 - Inclisiran (Total) | Percent Change in LDL-C From Baseline up to Day 720 | DAY 450 | -24.5 Percent change in LDL-C | Standard Deviation 26.45 |
| Part 2 - Inclisiran (Total) | Percent Change in LDL-C From Baseline up to Day 720 | DAY 510 | -32.5 Percent change in LDL-C | Standard Deviation 22.8 |
| Part 2 - Inclisiran (Total) | Percent Change in LDL-C From Baseline up to Day 720 | DAY 630 | -26.5 Percent change in LDL-C | Standard Deviation 24.33 |
| Part 2 - Inclisiran (Total) | Percent Change in LDL-C From Baseline up to Day 720 | Day 720 (study completion) | -33.7 Percent change in LDL-C | Standard Deviation 23.98 |
Secondary
Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)
Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to Day 330.
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1) | -5.04 Percent change in Lp(a) |
| Part 1 - Placebo | Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1) | 1.14 Percent change in Lp(a) |
p-value: 0.141995% CI: [-17.48, 5.12]ANCOVA
Secondary
Percent Change in Lp(a) From Baseline up to Day 720
Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 150 | -13.4 Percent change in Lp(a) | Standard Deviation 22.6 |
| Part 1- Inclisiran | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 360 | -9.3 Percent change in Lp(a) | Standard Deviation 28.44 |
| Part 1- Inclisiran | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 330 | -7.2 Percent change in Lp(a) | Standard Deviation 30.8 |
| Part 1 - Placebo | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 360 | 3.6 Percent change in Lp(a) | Standard Deviation 23.27 |
| Part 1 - Placebo | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 330 | 1.1 Percent change in Lp(a) | Standard Deviation 24.25 |
| Part 1 - Placebo | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 150 | 5.4 Percent change in Lp(a) | Standard Deviation 23.96 |
| Part 2 - Inclisiran (Total) | Percent Change in Lp(a) From Baseline up to Day 720 | Day 720 (study completion) | -4.2 Percent change in Lp(a) | Standard Deviation 163.74 |
| Part 2 - Inclisiran (Total) | Percent Change in Lp(a) From Baseline up to Day 720 | DAY 510 | -13.3 Percent change in Lp(a) | Standard Deviation 28.81 |
Secondary
Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)
Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to Day 330.
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1) | -25.04 Percent change in non-HDL-C |
| Part 1 - Placebo | Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1) | 1.76 Percent change in non-HDL-C |
p-value: <0.000195% CI: [-33.63, -19.97]ANCOVA
Secondary
Percent Change in Non-HDL-C From Baseline up to Day 720
Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 360 | -24.0 Percent change in non-HDL-C | Standard Deviation 21.74 |
| Part 1- Inclisiran | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 330 | -25.7 Percent change in non-HDL-C | Standard Deviation 21.69 |
| Part 1- Inclisiran | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 150 | -29.0 Percent change in non-HDL-C | Standard Deviation 20.15 |
| Part 1 - Placebo | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 330 | 1.8 Percent change in non-HDL-C | Standard Deviation 19.43 |
| Part 1 - Placebo | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 150 | 5.1 Percent change in non-HDL-C | Standard Deviation 24.85 |
| Part 1 - Placebo | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 360 | 1.2 Percent change in non-HDL-C | Standard Deviation 27.43 |
| Part 2 - Inclisiran (Total) | Percent Change in Non-HDL-C From Baseline up to Day 720 | Day 720 (study completion) | -31.0 Percent change in non-HDL-C | Standard Deviation 23.04 |
| Part 2 - Inclisiran (Total) | Percent Change in Non-HDL-C From Baseline up to Day 720 | DAY 510 | -29.9 Percent change in non-HDL-C | Standard Deviation 21.6 |
Secondary
Percent Change in PCSK9 From Baseline up to Day 720
Percentage change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 90 | -67.8 Percent change in PCSK9 | Standard Deviation 15.17 |
| Part 1- Inclisiran | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 150 | -72.3 Percent change in PCSK9 | Standard Deviation 11.37 |
| Part 1- Inclisiran | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 360 | -72.0 Percent change in PCSK9 | Standard Deviation 10.47 |
| Part 1- Inclisiran | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 330 | -72.9 Percent change in PCSK9 | Standard Deviation 12.12 |
| Part 1 - Placebo | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 90 | 11.6 Percent change in PCSK9 | Standard Deviation 46.61 |
| Part 1 - Placebo | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 150 | 3.8 Percent change in PCSK9 | Standard Deviation 36.95 |
| Part 1 - Placebo | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 330 | 4.8 Percent change in PCSK9 | Standard Deviation 34.5 |
| Part 1 - Placebo | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 360 | 11.7 Percent change in PCSK9 | Standard Deviation 57.77 |
| Part 2 - Inclisiran (Total) | Percent Change in PCSK9 From Baseline up to Day 720 | Day 720 (study completion) | -71.6 Percent change in PCSK9 | Standard Deviation 13.42 |
| Part 2 - Inclisiran (Total) | Percent Change in PCSK9 From Baseline up to Day 720 | DAY 510 | -74.3 Percent change in PCSK9 | Standard Deviation 10.46 |
Secondary
Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1)
Percentage change in total cholesterol from baseline to Day 330.
Time frame: Baseline and Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1) | -18.72 Percent change in total cholesterol |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1) | 0.48 Percent change in total cholesterol |
p-value: <0.000195% CI: [-24.65, -13.75]ANCOVA
Secondary
Percent Change in Total Cholesterol From Baseline up to Day 720
Percentage change in total cholesterol from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 150 | -22.6 Percent change in total cholesterol | Standard Deviation 15.77 |
| Part 1- Inclisiran | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 330 | -19.2 Percent change in total cholesterol | Standard Deviation 17.77 |
| Part 1- Inclisiran | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 360 | -18.5 Percent change in total cholesterol | Standard Deviation 17.18 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 330 | 0.6 Percent change in total cholesterol | Standard Deviation 15.46 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 360 | 0.6 Percent change in total cholesterol | Standard Deviation 21.81 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 150 | 4.4 Percent change in total cholesterol | Standard Deviation 20.49 |
| Part 2 - Inclisiran (Total) | Percent Change in Total Cholesterol From Baseline up to Day 720 | Day 720 (study completion) | -23.7 Percent change in total cholesterol | Standard Deviation 18.29 |
| Part 2 - Inclisiran (Total) | Percent Change in Total Cholesterol From Baseline up to Day 720 | DAY 510 | -23.0 Percent change in total cholesterol | Standard Deviation 17.5 |
Secondary
Percent Change in Triglycerides From Baseline up to Day 720
Percentage change in triglycerides from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 150 | 16.2 Percent change in triglycerides | Standard Deviation 78.18 |
| Part 1- Inclisiran | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 330 | 1.8 Percent change in triglycerides | Standard Deviation 38.39 |
| Part 1- Inclisiran | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 360 | 1.7 Percent change in triglycerides | Standard Deviation 40.03 |
| Part 1 - Placebo | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 330 | 9.7 Percent change in triglycerides | Standard Deviation 43.04 |
| Part 1 - Placebo | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 360 | 3.8 Percent change in triglycerides | Standard Deviation 35.76 |
| Part 1 - Placebo | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 150 | 2.8 Percent change in triglycerides | Standard Deviation 37.44 |
| Part 2 - Inclisiran (Total) | Percent Change in Triglycerides From Baseline up to Day 720 | DAY 510 | 3.4 Percent change in triglycerides | Standard Deviation 43.08 |
| Part 2 - Inclisiran (Total) | Percent Change in Triglycerides From Baseline up to Day 720 | Day 720 (study completion) | 1.9 Percent change in triglycerides | Standard Deviation 41.84 |
Secondary
Percent Change in VLDL-C From Baseline up to Day 720
Percentage change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Time frame: Baseline, up to Day 720
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization. At each time point, only subjects with a value at both baseline and that time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Inclisiran | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 330 | 0.6 Percent change in VLDL-C | Standard Deviation 39 |
| Part 1- Inclisiran | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 150 | 11.8 Percent change in VLDL-C | Standard Deviation 60.04 |
| Part 1- Inclisiran | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 360 | 1.0 Percent change in VLDL-C | Standard Deviation 40.15 |
| Part 1 - Placebo | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 360 | 4.7 Percent change in VLDL-C | Standard Deviation 35.65 |
| Part 1 - Placebo | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 150 | 3.3 Percent change in VLDL-C | Standard Deviation 38.25 |
| Part 1 - Placebo | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 330 | 10.0 Percent change in VLDL-C | Standard Deviation 42.29 |
| Part 2 - Inclisiran (Total) | Percent Change in VLDL-C From Baseline up to Day 720 | Day 720 (study completion) | 1.9 Percent change in VLDL-C | Standard Deviation 42.2 |
| Part 2 - Inclisiran (Total) | Percent Change in VLDL-C From Baseline up to Day 720 | DAY 510 | 1.4 Percent change in VLDL-C | Standard Deviation 41.13 |
Secondary
Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)
Time-adjusted percent change in LDL-C (after Day 90 and up to Day 330), calculated as the average of percent changes from baseline to Days 150, 270 and 330
Time frame: Baseline, after Day 90 up to Day 330
Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1- Inclisiran | Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1) | -26.04 Time-adjusted percent change in LDL-C |
| Part 1 - Placebo | Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1) | 3.26 Time-adjusted percent change in LDL-C |
p-value: <0.000195% CI: [-36.24, -22.36]MMRM