Trial Outcomes & Findings for A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (NCT NCT02963311)

NCT ID: NCT02963311

Last Updated: 2020-05-18

Results Overview

Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: Day 1, Day 90
• Results posted on: 2020-05-18

Participant Flow

Participant milestones

Measure	Inclisiran 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Overall Study STARTED	9
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Inclisiran 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Overall Study Withdrawal by Subject	1
Overall Study Screen Failure	4

Baseline Characteristics

A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

Baseline characteristics by cohort

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	37.0 years STANDARD_DEVIATION 13.04 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants
Region of Enrollment South Africa	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1, Day 90

Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.

Outcome measures

Measure

Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

Percentage Change From Day 1 to Day 90 in LDL-C

-12.26 percent change Interval -43.75 to 19.24

PRIMARY outcome

Timeframe: Day 1, Day 180 (or Final Visit)

Outcome measures

Measure

Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C

-20.96 percent change Interval -49.97 to 8.05

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C Day 90	-56.3 mg/dL Standard Deviation 115.18
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C Day 180	-105.3 mg/dL Standard Deviation 116.44

SECONDARY outcome

Timeframe: Day 1, Day 60, Day 90

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 Day 60	-64.9 percent change Standard Deviation 18.33
Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 Day 90	-59.0 percent change Standard Deviation 16.46

SECONDARY outcome

Timeframe: Day 1, Day 60, Day 90

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 Day 60	-654.1 ng/mL Standard Deviation 564.67
Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 Day 90	-602.3 ng/mL Standard Deviation 559.61

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol Day 180	-19.8 percent change Standard Deviation 13.68
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol Day 90	-13.9 percent change Standard Deviation 14.84

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol Day 90	-77.8 mg/dL Standard Deviation 103.41
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol Day 180	-118.0 mg/dL Standard Deviation 103.52

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides Day 90	-21.0 percent change Standard Deviation 30.99
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides Day 180	-20.13 percent change Standard Deviation 11.67

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides Day 90	-35.5 mg/dL Standard Deviation 38.76
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides Day 180	-26.3 mg/dL Standard Deviation 24.64

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C Day 90	-12.1 percent change Standard Deviation 17.98
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C Day 180	-19.8 percent change Standard Deviation 11.78

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C Day 90	-6.0 mg/dL Standard Deviation 9.13
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C Day 180	-9.5 mg/dL Standard Deviation 4.73

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C Day 90	-13.9 percent change Standard Deviation 14.78
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C Day 180	-19.7 percent change Standard Deviation 13.93

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C Day 90	-71.8 mg/dL Standard Deviation 97.70
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C Day 180	-108.5 mg/dL Standard Deviation 99.38

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C Day 90	8.5 percent change Standard Deviation 65.28
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C Day 180	55.5 percent change Standard Deviation 131.92

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C Day 90	-15.5 mg/dL Standard Deviation 28.41
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C Day 180	-3.3 mg/dL Standard Deviation 37.32

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 Day 90	-8.3 percent change Standard Deviation 12.95
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 Day 180	-14.2 percent change Standard Deviation 14.44

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 Day 90	-11.5 mg/dL Standard Deviation 17.52
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 Day 180	-19.8 mg/dL Standard Deviation 19.00

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B Day 90	-26.6 percent change Standard Deviation 14.98
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B Day 180	-25.0 percent change Standard Deviation 14.50

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B Day 90	-95.3 mg/dL Standard Deviation 78.16
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B Day 180	-86.3 mg/dL Standard Deviation 72.02

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

The reported percent change value is the per participant calculated Mean.

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a Day 90	-3.5 percent change Standard Deviation 15.70
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a Day 180	-11.8 percent change Standard Deviation 15.15

SECONDARY outcome

Timeframe: Day 1, Day 90, Day 180 (or Final Visit)

Outcome measures

Measure	Inclisiran n=4 Participants 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a Day 90	13.5 nmol/L Standard Deviation 21.92
Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a Day 180	-23.8 nmol/L Standard Deviation 52.73

Adverse Events

Inclisiran

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure

Inclisiran n=4 participants at risk 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

Cardiac disorders Angina unstable

25.0% 1/4 • Number of events 1 • 18 months

Other adverse events

Measure	Inclisiran n=4 participants at risk 300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
Cardiac disorders Angina unstable	25.0% 1/4 • 18 months
Gastrointestinal disorders Abdominal pain upper	25.0% 1/4 • 18 months
General disorders Influenza like illness	25.0% 1/4 • 18 months
General disorders Non-cardiac chest pain	25.0% 1/4 • 18 months
Infections and infestations Cystitis	25.0% 1/4 • 18 months
Infections and infestations Nasopharyngitis	25.0% 1/4 • 18 months
Injury, poisoning and procedural complications Limb injury	25.0% 1/4 • 18 months
Injury, poisoning and procedural complications Road traffic accident	25.0% 1/4 • 18 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	25.0% 1/4 • 18 months
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • 18 months
Nervous system disorders Paraesthesia	25.0% 1/4 • 18 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • 18 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	25.0% 1/4 • 18 months
Skin and subcutaneous tissue disorders Acne	25.0% 1/4 • 18 months

Additional Information

Frank Bosley, Vice-President, Regulatory Operaions

The Medicines Company

Phone: 9732906016

Email: frank.bosley@themedco.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place