Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia (NCT NCT04652726)
NCT ID: NCT04652726
Last Updated: 2026-01-13
Results Overview
Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
141 participants
Primary outcome timeframe
Baseline and Day 330
Results posted on
2026-01-13
Participant Flow
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).
The study had an approximately 4-week screening/run-in period
Participant milestones
| Measure |
Part 1- Inclisiran
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360
|
|---|---|---|---|
|
Part 1 (Double-blind Period)
STARTED
|
93
|
48
|
0
|
|
Part 1 (Double-blind Period)
COMPLETED
|
91
|
48
|
0
|
|
Part 1 (Double-blind Period)
NOT COMPLETED
|
2
|
0
|
0
|
|
Part 2 (Open-label Period)
STARTED
|
0
|
0
|
139
|
|
Part 2 (Open-label Period)
COMPLETED
|
0
|
0
|
139
|
|
Part 2 (Open-label Period)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part 1- Inclisiran
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360
|
|---|---|---|---|
|
Part 1 (Double-blind Period)
Physician Decision
|
1
|
0
|
0
|
|
Part 1 (Double-blind Period)
Participant/guardian decision
|
1
|
0
|
0
|
Baseline Characteristics
Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia
Baseline characteristics by cohort
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Total
n=141 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
93 Participants
n=210 Participants
|
48 Participants
n=19 Participants
|
141 Participants
n=123 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
|
Age, Continuous
|
15.2 years
STANDARD_DEVIATION 2.02 • n=210 Participants
|
14.9 years
STANDARD_DEVIATION 1.80 • n=19 Participants
|
15.1 years
STANDARD_DEVIATION 1.94 • n=123 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=210 Participants
|
24 Participants
n=19 Participants
|
75 Participants
n=123 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=210 Participants
|
24 Participants
n=19 Participants
|
66 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
4 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
5 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
4 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
White
|
80 Participants
n=210 Participants
|
48 Participants
n=19 Participants
|
128 Participants
n=123 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization.
Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)
|
-27.14 percent change in LDL-C
Interval -32.04 to -22.24
|
1.40 percent change in LDL-C
Interval -3.97 to 6.78
|
—
|
SECONDARY outcome
Timeframe: Baseline, after Day 90 up to Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
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
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
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
Interval -30.11 to -21.98
|
3.26 Time-adjusted percent change in LDL-C
Interval -2.37 to 8.89
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
Absolute change in LDL-C from baseline to Day 330.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)
|
-50.54 mg/dL
Interval -59.22 to -41.86
|
-0.55 mg/dL
Interval -10.48 to 9.38
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
Percentage change in apolipoprotein B (Apo B) from baseline to Day 330.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)
|
-21.46 Percent change in Apo B
Interval -25.59 to -17.33
|
4.24 Percent change in Apo B
Interval -0.07 to 8.56
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to Day 330.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)
|
-5.04 Percent change in Lp(a)
Interval -14.21 to 4.13
|
1.14 Percent change in Lp(a)
Interval -5.48 to 7.77
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to Day 330.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)
|
-25.04 Percent change in non-HDL-C
Interval -29.68 to -20.41
|
1.76 Percent change in non-HDL-C
Interval -3.25 to 6.77
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 330Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned by randomization
Percentage change in total cholesterol from baseline to Day 330.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1)
|
-18.72 Percent change in total cholesterol
Interval -22.48 to -14.96
|
0.48 Percent change in total cholesterol
Interval -3.46 to 4.42
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in LDL-C from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
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
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
-32.5 Percent change in LDL-C
Standard Deviation 22.80
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 630
|
—
|
—
|
-26.5 Percent change in LDL-C
Standard Deviation 24.33
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 150
|
-32.5 Percent change in LDL-C
Standard Deviation 21.47
|
6.4 Percent change in LDL-C
Standard Deviation 28.83
|
—
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 270
|
-19.0 Percent change in LDL-C
Standard Deviation 28.31
|
2.1 Percent change in LDL-C
Standard Deviation 22.44
|
—
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 330
|
-27.8 Percent change in LDL-C
Standard Deviation 22.95
|
1.5 Percent change in LDL-C
Standard Deviation 20.59
|
—
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 360
|
-26.1 Percent change in LDL-C
Standard Deviation 22.71
|
1.5 Percent change in LDL-C
Standard Deviation 30.56
|
—
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 450
|
—
|
—
|
-24.5 Percent change in LDL-C
Standard Deviation 26.45
|
|
Percent Change in LDL-C From Baseline up to Day 720
DAY 90
|
-23.9 Percent change in LDL-C
Standard Deviation 22.14
|
-0.1 Percent change in LDL-C
Standard Deviation 20.16
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in LDL-C from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=93 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 90
|
-45.4 mg/dL
Standard Deviation 45.26
|
-3.0 mg/dL
Standard Deviation 35.02
|
—
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 150
|
-61.0 mg/dL
Standard Deviation 45.84
|
6.6 mg/dL
Standard Deviation 46.22
|
—
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 270
|
-38.4 mg/dL
Standard Deviation 55.77
|
1.0 mg/dL
Standard Deviation 36.92
|
—
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 330
|
-51.9 mg/dL
Standard Deviation 45.47
|
-0.3 mg/dL
Standard Deviation 38.04
|
—
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 360
|
-49.0 mg/dL
Standard Deviation 44.49
|
-2.9 mg/dL
Standard Deviation 51.74
|
—
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 450
|
—
|
—
|
-46.3 mg/dL
Standard Deviation 52.51
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
-60.8 mg/dL
Standard Deviation 48.88
|
|
Absolute Change in LDL-C From Baseline up to Day 720
DAY 630
|
—
|
—
|
-50.9 mg/dL
Standard Deviation 50.30
|
|
Absolute Change in LDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-64.1 mg/dL
Standard Deviation 53.91
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Apo B From Baseline up to Day 720
DAY 150
|
-25.1 Percent change in Apo B
Standard Deviation 18.18
|
2.2 Percent change in Apo B
Standard Deviation 20.77
|
—
|
|
Percent Change in Apo B From Baseline up to Day 720
DAY 330
|
-21.9 Percent change in Apo B
Standard Deviation 19.51
|
3.9 Percent change in Apo B
Standard Deviation 18.13
|
—
|
|
Percent Change in Apo B From Baseline up to Day 720
DAY 360
|
-19.3 Percent change in Apo B
Standard Deviation 21.36
|
1.7 Percent change in Apo B
Standard Deviation 22.70
|
—
|
|
Percent Change in Apo B From Baseline up to Day 720
DAY 510
|
—
|
—
|
-24.5 Percent change in Apo B
Standard Deviation 21.77
|
|
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
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Apo B From Baseline up to Day 720
DAY 150
|
-33.3 mg/dL
Standard Deviation 28.20
|
0.0 mg/dL
Standard Deviation 27.38
|
—
|
|
Absolute Change in Apo B From Baseline up to Day 720
DAY 330
|
-29.2 mg/dL
Standard Deviation 28.04
|
2.9 mg/dL
Standard Deviation 23.47
|
—
|
|
Absolute Change in Apo B From Baseline up to Day 720
DAY 360
|
-26.1 mg/dL
Standard Deviation 29.59
|
-0.6 mg/dL
Standard Deviation 28.72
|
—
|
|
Absolute Change in Apo B From Baseline up to Day 720
DAY 510
|
—
|
—
|
-33.5 mg/dL
Standard Deviation 32.13
|
|
Absolute Change in Apo B From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-35.4 mg/dL
Standard Deviation 33.83
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Lp(a) From Baseline up to Day 720
DAY 150
|
-13.4 Percent change in Lp(a)
Standard Deviation 22.60
|
5.4 Percent change in Lp(a)
Standard Deviation 23.96
|
—
|
|
Percent Change in Lp(a) From Baseline up to Day 720
DAY 330
|
-7.2 Percent change in Lp(a)
Standard Deviation 30.80
|
1.1 Percent change in Lp(a)
Standard Deviation 24.25
|
—
|
|
Percent Change in Lp(a) From Baseline up to Day 720
DAY 360
|
-9.3 Percent change in Lp(a)
Standard Deviation 28.44
|
3.6 Percent change in Lp(a)
Standard Deviation 23.27
|
—
|
|
Percent Change in Lp(a) From Baseline up to Day 720
DAY 510
|
—
|
—
|
-13.3 Percent change in Lp(a)
Standard Deviation 28.81
|
|
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
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in lipoprotein (a) \[Lp(a)\] from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Lp(a) From Baseline up to Day 720
DAY 150
|
-12.5 nmol/L
Standard Deviation 34.73
|
3.2 nmol/L
Standard Deviation 20.67
|
—
|
|
Absolute Change in Lp(a) From Baseline up to Day 720
DAY 330
|
-9.5 nmol/L
Standard Deviation 33.81
|
5.3 nmol/L
Standard Deviation 21.55
|
—
|
|
Absolute Change in Lp(a) From Baseline up to Day 720
DAY 360
|
-10.2 nmol/L
Standard Deviation 31.16
|
4.4 nmol/L
Standard Deviation 22.99
|
—
|
|
Absolute Change in Lp(a) From Baseline up to Day 720
DAY 510
|
—
|
—
|
-10.1 nmol/L
Standard Deviation 34.98
|
|
Absolute Change in Lp(a) From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-9.0 nmol/L
Standard Deviation 50.08
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
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
|
5.1 Percent change in non-HDL-C
Standard Deviation 24.85
|
—
|
|
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
|
1.8 Percent change in non-HDL-C
Standard Deviation 19.43
|
—
|
|
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
|
1.2 Percent change in non-HDL-C
Standard Deviation 27.43
|
—
|
|
Percent Change in Non-HDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
-29.9 Percent change in non-HDL-C
Standard Deviation 21.60
|
|
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
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Non-HDL-C From Baseline up to Day 720
DAY 150
|
-60.2 mg/dL
Standard Deviation 47.41
|
5.7 mg/dL
Standard Deviation 47.61
|
—
|
|
Absolute Change in Non-HDL-C From Baseline up to Day 720
DAY 330
|
-52.6 mg/dL
Standard Deviation 46.93
|
0.5 mg/dL
Standard Deviation 39.20
|
—
|
|
Absolute Change in Non-HDL-C From Baseline up to Day 720
DAY 360
|
-49.7 mg/dL
Standard Deviation 46.30
|
-3.0 mg/dL
Standard Deviation 52.75
|
—
|
|
Absolute Change in Non-HDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
-62.0 mg/dL
Standard Deviation 51.09
|
|
Absolute Change in Non-HDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-65.1 mg/dL
Standard Deviation 56.16
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in total cholesterol from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Total Cholesterol From Baseline up to Day 720
DAY 330
|
-19.2 Percent change in total cholesterol
Standard Deviation 17.77
|
0.6 Percent change in total cholesterol
Standard Deviation 15.46
|
—
|
|
Percent Change in Total Cholesterol From Baseline up to Day 720
DAY 360
|
-18.5 Percent change in total cholesterol
Standard Deviation 17.18
|
0.6 Percent change in total cholesterol
Standard Deviation 21.81
|
—
|
|
Percent Change in Total Cholesterol From Baseline up to Day 720
DAY 510
|
—
|
—
|
-23.0 Percent change in total cholesterol
Standard Deviation 17.50
|
|
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
|
|
Percent Change in Total Cholesterol From Baseline up to Day 720
DAY 150
|
-22.6 Percent change in total cholesterol
Standard Deviation 15.77
|
4.4 Percent change in total cholesterol
Standard Deviation 20.49
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in total cholesterol from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Total Cholesterol From Baseline up to Day 720
DAY 150
|
-59.0 mg/dL
Standard Deviation 47.79
|
6.6 mg/dL
Standard Deviation 48.08
|
—
|
|
Absolute Change in Total Cholesterol From Baseline up to Day 720
DAY 510
|
—
|
—
|
-59.6 mg/dL
Standard Deviation 51.06
|
|
Absolute Change in Total Cholesterol From Baseline up to Day 720
DAY 330
|
-49.4 mg/dL
Standard Deviation 47.77
|
-0.9 mg/dL
Standard Deviation 38.48
|
—
|
|
Absolute Change in Total Cholesterol From Baseline up to Day 720
DAY 360
|
-48.2 mg/dL
Standard Deviation 47.06
|
-3.1 mg/dL
Standard Deviation 52.66
|
—
|
|
Absolute Change in Total Cholesterol From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-62.3 mg/dL
Standard Deviation 55.05
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in triglycerides from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Triglycerides From Baseline up to Day 720
DAY 330
|
1.8 Percent change in triglycerides
Standard Deviation 38.39
|
9.7 Percent change in triglycerides
Standard Deviation 43.04
|
—
|
|
Percent Change in Triglycerides From Baseline up to Day 720
DAY 360
|
1.7 Percent change in triglycerides
Standard Deviation 40.03
|
3.8 Percent change in triglycerides
Standard Deviation 35.76
|
—
|
|
Percent Change in Triglycerides From Baseline up to Day 720
DAY 510
|
—
|
—
|
3.4 Percent change in triglycerides
Standard Deviation 43.08
|
|
Percent Change in Triglycerides From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
1.9 Percent change in triglycerides
Standard Deviation 41.84
|
|
Percent Change in Triglycerides From Baseline up to Day 720
DAY 150
|
16.2 Percent change in triglycerides
Standard Deviation 78.18
|
2.8 Percent change in triglycerides
Standard Deviation 37.44
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in triglycerides from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Triglycerides From Baseline up to Day 720
DAY 150
|
6.9 mg/dL
Standard Deviation 64.67
|
-4.8 mg/dL
Standard Deviation 31.53
|
—
|
|
Absolute Change in Triglycerides From Baseline up to Day 720
DAY 330
|
-2.9 mg/dL
Standard Deviation 35.01
|
3.5 mg/dL
Standard Deviation 35.55
|
—
|
|
Absolute Change in Triglycerides From Baseline up to Day 720
DAY 360
|
-3.1 mg/dL
Standard Deviation 38.13
|
-1.7 mg/dL
Standard Deviation 28.47
|
—
|
|
Absolute Change in Triglycerides From Baseline up to Day 720
DAY 510
|
—
|
—
|
-4.2 mg/dL
Standard Deviation 34.70
|
|
Absolute Change in Triglycerides From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-4.8 mg/dL
Standard Deviation 36.21
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in HDL-C From Baseline up to Day 720
DAY 330
|
7.4 Percent change in HDL-C
Standard Deviation 19.15
|
-1.9 Percent change in HDL-C
Standard Deviation 16.15
|
—
|
|
Percent Change in HDL-C From Baseline up to Day 720
DAY 360
|
4.4 Percent change in HDL-C
Standard Deviation 19.54
|
0.9 Percent change in HDL-C
Standard Deviation 12.39
|
—
|
|
Percent Change in HDL-C From Baseline up to Day 720
DAY 150
|
3.6 Percent change in HDL-C
Standard Deviation 18.88
|
3.6 Percent change in HDL-C
Standard Deviation 16.49
|
—
|
|
Percent Change in HDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
6.6 Percent change in HDL-C
Standard Deviation 19.84
|
|
Percent Change in HDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
7.4 Percent change in HDL-C
Standard Deviation 20.40
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in HDL-C From Baseline up to Day 720
DAY 150
|
1.2 mg/dL
Standard Deviation 10.23
|
0.9 mg/dL
Standard Deviation 8.07
|
—
|
|
Absolute Change in HDL-C From Baseline up to Day 720
DAY 330
|
3.2 mg/dL
Standard Deviation 9.57
|
-1.4 mg/dL
Standard Deviation 7.77
|
—
|
|
Absolute Change in HDL-C From Baseline up to Day 720
DAY 360
|
1.5 mg/dL
Standard Deviation 9.59
|
-0.1 mg/dL
Standard Deviation 6.23
|
—
|
|
Absolute Change in HDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
2.4 mg/dL
Standard Deviation 9.32
|
|
Absolute Change in HDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
2.8 mg/dL
Standard Deviation 9.75
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in VLDL-C From Baseline up to Day 720
DAY 150
|
11.8 Percent change in VLDL-C
Standard Deviation 60.04
|
3.3 Percent change in VLDL-C
Standard Deviation 38.25
|
—
|
|
Percent Change in VLDL-C From Baseline up to Day 720
DAY 330
|
0.6 Percent change in VLDL-C
Standard Deviation 39.00
|
10.0 Percent change in VLDL-C
Standard Deviation 42.29
|
—
|
|
Percent Change in VLDL-C From Baseline up to Day 720
DAY 360
|
1.0 Percent change in VLDL-C
Standard Deviation 40.15
|
4.7 Percent change in VLDL-C
Standard Deviation 35.65
|
—
|
|
Percent Change in VLDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
1.4 Percent change in VLDL-C
Standard Deviation 41.13
|
|
Percent Change in VLDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
1.9 Percent change in VLDL-C
Standard Deviation 42.20
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolut Change in VLDL-C From Baseline up to Day 720
DAY 150
|
0.7 mg/dL
Standard Deviation 10.02
|
-0.9 mg/dL
Standard Deviation 6.37
|
—
|
|
Absolut Change in VLDL-C From Baseline up to Day 720
DAY 330
|
-0.7 mg/dL
Standard Deviation 7.04
|
0.8 mg/dL
Standard Deviation 7.07
|
—
|
|
Absolut Change in VLDL-C From Baseline up to Day 720
DAY 360
|
-0.7 mg/dL
Standard Deviation 7.63
|
-0.2 mg/dL
Standard Deviation 5.66
|
—
|
|
Absolut Change in VLDL-C From Baseline up to Day 720
DAY 510
|
—
|
—
|
-1.2 mg/dL
Standard Deviation 6.90
|
|
Absolut Change in VLDL-C From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-1.0 mg/dL
Standard Deviation 7.40
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in Apo A1 From Baseline up to Day 720
DAY 150
|
3.7 Percent change in Apo A1
Standard Deviation 15.40
|
0.4 Percent change in Apo A1
Standard Deviation 13.22
|
—
|
|
Percent Change in Apo A1 From Baseline up to Day 720
DAY 330
|
5.2 Percent change in Apo A1
Standard Deviation 14.49
|
-1.5 Percent change in Apo A1
Standard Deviation 10.58
|
—
|
|
Percent Change in Apo A1 From Baseline up to Day 720
DAY 360
|
3.0 Percent change in Apo A1
Standard Deviation 15.12
|
-1.5 Percent change in Apo A1
Standard Deviation 9.98
|
—
|
|
Percent Change in Apo A1 From Baseline up to Day 720
DAY 510
|
—
|
—
|
6.3 Percent change in Apo A1
Standard Deviation 16.19
|
|
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 outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=92 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolute Change in Apo A1 From Baseline up to Day 720
DAY 150
|
3.3 mg/dL
Standard Deviation 21.76
|
0.0 mg/dL
Standard Deviation 17.72
|
—
|
|
Absolute Change in Apo A1 From Baseline up to Day 720
DAY 360
|
2.7 mg/dL
Standard Deviation 21.87
|
-2.6 mg/dL
Standard Deviation 13.89
|
—
|
|
Absolute Change in Apo A1 From Baseline up to Day 720
DAY 510
|
—
|
—
|
7.5 mg/dL
Standard Deviation 22.24
|
|
Absolute Change in Apo A1 From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
5.4 mg/dL
Standard Deviation 21.61
|
|
Absolute Change in Apo A1 From Baseline up to Day 720
DAY 330
|
6.1 mg/dL
Standard Deviation 21.16
|
-2.8 mg/dL
Standard Deviation 14.24
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Percentage change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=90 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=136 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Percent Change in PCSK9 From Baseline up to Day 720
DAY 90
|
-67.8 Percent change in PCSK9
Standard Deviation 15.17
|
11.6 Percent change in PCSK9
Standard Deviation 46.61
|
—
|
|
Percent Change in PCSK9 From Baseline up to Day 720
DAY 150
|
-72.3 Percent change in PCSK9
Standard Deviation 11.37
|
3.8 Percent change in PCSK9
Standard Deviation 36.95
|
—
|
|
Percent Change in PCSK9 From Baseline up to Day 720
DAY 330
|
-72.9 Percent change in PCSK9
Standard Deviation 12.12
|
4.8 Percent change in PCSK9
Standard Deviation 34.50
|
—
|
|
Percent Change in PCSK9 From Baseline up to Day 720
DAY 360
|
-72.0 Percent change in PCSK9
Standard Deviation 10.47
|
11.7 Percent change in PCSK9
Standard Deviation 57.77
|
—
|
|
Percent Change in PCSK9 From Baseline up to Day 720
DAY 510
|
—
|
—
|
-74.3 Percent change in PCSK9
Standard Deviation 10.46
|
|
Percent Change in PCSK9 From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-71.6 Percent change in PCSK9
Standard Deviation 13.42
|
SECONDARY outcome
Timeframe: Baseline, up to Day 720Population: 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.
Absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
Outcome measures
| Measure |
Part 1- Inclisiran
n=90 Participants
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 Participants
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=136 Participants
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Absolut Change in PCSK9 From Baseline up to Day 720
DAY 90
|
-259.6 ng/mL
Standard Deviation 121.5
|
2.1 ng/mL
Standard Deviation 223.16
|
—
|
|
Absolut Change in PCSK9 From Baseline up to Day 720
DAY 150
|
-274.8 ng/mL
Standard Deviation 116.2
|
-27.7 ng/mL
Standard Deviation 210.44
|
—
|
|
Absolut Change in PCSK9 From Baseline up to Day 720
DAY 330
|
-278.2 ng/mL
Standard Deviation 119.8
|
-23.9 ng/mL
Standard Deviation 210.85
|
—
|
|
Absolut Change in PCSK9 From Baseline up to Day 720
DAY 360
|
-275.4 ng/mL
Standard Deviation 117.2
|
-9.1 ng/mL
Standard Deviation 245.36
|
—
|
|
Absolut Change in PCSK9 From Baseline up to Day 720
DAY 510
|
—
|
—
|
-288.1 ng/mL
Standard Deviation 156.9
|
|
Absolut Change in PCSK9 From Baseline up to Day 720
Day 720 (study completion)
|
—
|
—
|
-279.5 ng/mL
Standard Deviation 159.2
|
Adverse Events
Part 1 - Inclisiran
Serious events: 3 serious events
Other events: 57 other events
Deaths: 0 deaths
Part 1 - Placebo
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Part 2 - Inclisiran (Total)
Serious events: 6 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part 1 - Inclisiran
n=93 participants at risk
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 participants at risk
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 participants at risk
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Immune system disorders
Anaphylactic reaction
|
1.1%
1/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Dengue fever
|
1.1%
1/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Nervous system disorders
Status migrainosus
|
1.1%
1/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Nervous system disorders
Syncope
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Vascular disorders
Varicose vein
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
Other adverse events
| Measure |
Part 1 - Inclisiran
n=93 participants at risk
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
|
Part 1 - Placebo
n=48 participants at risk
Placebo sc injection (given at Day 1, 90 and 270)
|
Part 2 - Inclisiran (Total)
n=139 participants at risk
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
|
|---|---|---|---|
|
Nervous system disorders
Syncope
|
5.4%
5/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
General disorders
Fatigue
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Gastrointestinal disorders
Nausea
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.9%
4/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Gastrointestinal disorders
Vomiting
|
5.4%
5/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
General disorders
Influenza like illness
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
6.2%
3/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
1.4%
2/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
General disorders
Injection site pain
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.2%
2/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.9%
4/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
General disorders
Injection site reaction
|
8.6%
8/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
3.6%
5/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
General disorders
Malaise
|
0.00%
0/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.2%
2/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
COVID-19
|
18.3%
17/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
25.0%
12/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
5.0%
7/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Gastroenteritis
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.2%
3/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Influenza
|
10.8%
10/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
12.5%
6/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
7.9%
11/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Nasopharyngitis
|
14.0%
13/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
18.8%
9/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
10.1%
14/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Pharyngitis
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.2%
2/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.5%
6/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.2%
2/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.9%
4/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
3.2%
3/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
2.1%
1/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.72%
1/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Nervous system disorders
Headache
|
12.9%
12/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
6.2%
3/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.3%
6/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Nervous system disorders
Migraine
|
4.3%
4/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
0.00%
0/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
1.4%
2/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.2%
3/93 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.2%
2/48 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
4.3%
6/139 • Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
|
Additional Information
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