Trial Outcomes & Findings for Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2 (NCT NCT01763918)

NCT ID: NCT01763918

Last Updated: 2019-06-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 331 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2019-06-17

Participant Flow

Men and women 18 to 80 years old with a diagnosis of heterozygous familial hypercholesterolemia (HeFH) on stable doses of an approved statin with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL were eligible for this study. The first participant enrolled on 07 February 2013 and the last participant enrolled 03 September 2013.

Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by LDL-C level (< 160 mg/dL vs ≥ 160 mg/dL) and ezetimibe use.

Participant milestones

Measure	Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Study STARTED	55	55	111	110
Overall Study Received Treatment	54	55	110	110
Overall Study COMPLETED	49	54	101	108
Overall Study NOT COMPLETED	6	1	10	2

Reasons for withdrawal

Measure	Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Overall Study Withdrawal by Subject	2	1	1	2
Overall Study Sponsor Decision	4	0	9	0

Baseline Characteristics

Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2

Baseline characteristics by cohort

Measure	Placebo Q2W n=55 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=111 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.	Total n=331 Participants Total of all reporting groups
Age, Continuous	51.1 years STANDARD_DEVIATION 14.1 • n=5 Participants	46.8 years STANDARD_DEVIATION 12.1 • n=7 Participants	52.3 years STANDARD_DEVIATION 12.6 • n=5 Participants	51.9 years STANDARD_DEVIATION 12.0 • n=4 Participants	51.1 years STANDARD_DEVIATION 12.7 • n=21 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants	46 Participants n=4 Participants	140 Participants n=21 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants	64 Participants n=4 Participants	191 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	8 participants n=4 Participants	16 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Race/Ethnicity, Customized White	51 participants n=5 Participants	49 participants n=7 Participants	100 participants n=5 Participants	98 participants n=4 Participants	298 participants n=21 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	3 participants n=4 Participants	14 participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	54 participants n=5 Participants	55 participants n=7 Participants	111 participants n=5 Participants	109 participants n=4 Participants	329 participants n=21 Participants
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level < 160 mg/dL	35 participants n=5 Participants	35 participants n=7 Participants	70 participants n=5 Participants	70 participants n=4 Participants	210 participants n=21 Participants
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level ≥ 160 mg/dL	20 participants n=5 Participants	20 participants n=7 Participants	41 participants n=5 Participants	40 participants n=4 Participants	121 participants n=21 Participants
Baseline Ezetimibe Use No	22 participants n=5 Participants	21 participants n=7 Participants	43 participants n=5 Participants	43 participants n=4 Participants	129 participants n=21 Participants
Baseline Ezetimibe Use Yes	33 participants n=5 Participants	34 participants n=7 Participants	68 participants n=5 Participants	67 participants n=4 Participants	202 participants n=21 Participants
LDL-C Concentration	151.1 mg/dL STANDARD_DEVIATION 36.5 • n=5 Participants	151.5 mg/dL STANDARD_DEVIATION 42.5 • n=7 Participants	161.4 mg/dL STANDARD_DEVIATION 51.0 • n=5 Participants	153.6 mg/dL STANDARD_DEVIATION 43.3 • n=4 Participants	155.5 mg/dL STANDARD_DEVIATION 44.9 • n=21 Participants
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration	175.4 mg/dL STANDARD_DEVIATION 43.9 • n=5 Participants	175.4 mg/dL STANDARD_DEVIATION 45.9 • n=7 Participants	187.4 mg/dL STANDARD_DEVIATION 56.7 • n=5 Participants	178.5 mg/dL STANDARD_DEVIATION 45.8 • n=4 Participants	180.4 mg/dL STANDARD_DEVIATION 49.5 • n=21 Participants
Apolipoprotein B Concentration	114.3 mg/dL STANDARD_DEVIATION 29.8 • n=5 Participants	110.3 mg/dL STANDARD_DEVIATION 21.7 • n=7 Participants	119.0 mg/dL STANDARD_DEVIATION 30.7 • n=5 Participants	114.9 mg/dL STANDARD_DEVIATION 25.5 • n=4 Participants	115.4 mg/dL STANDARD_DEVIATION 27.5 • n=21 Participants
Total cholesterol/HDL-C Ratio	4.695 ratio STANDARD_DEVIATION 1.905 • n=5 Participants	4.844 ratio STANDARD_DEVIATION 1.435 • n=7 Participants	5.159 ratio STANDARD_DEVIATION 2.031 • n=5 Participants	4.842 ratio STANDARD_DEVIATION 1.801 • n=4 Participants	4.924 ratio STANDARD_DEVIATION 1.845 • n=21 Participants
Apolipoprotein B/Apolipoprotein A1 Ratio	0.815 ratio STANDARD_DEVIATION 0.264 • n=5 Participants	0.851 ratio STANDARD_DEVIATION 0.249 • n=7 Participants	0.888 ratio STANDARD_DEVIATION 0.322 • n=5 Participants	0.850 ratio STANDARD_DEVIATION 0.331 • n=4 Participants	0.857 ratio STANDARD_DEVIATION 0.305 • n=21 Participants
Lipoprotein(a) Concentration	44.0 nmol/L n=5 Participants	87.0 nmol/L n=7 Participants	77.5 nmol/L n=5 Participants	61.0 nmol/L n=4 Participants	65.0 nmol/L n=21 Participants
Triglyceride Concentration	95.8 mg/dL n=5 Participants	102.0 mg/dL n=7 Participants	118.5 mg/dL n=5 Participants	112.5 mg/dL n=4 Participants	110.0 mg/dL n=21 Participants
Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration	23.1 mg/dL STANDARD_DEVIATION 10.7 • n=5 Participants	23.9 mg/dL STANDARD_DEVIATION 10.5 • n=7 Participants	25.9 mg/dL STANDARD_DEVIATION 11.8 • n=5 Participants	24.9 mg/dL STANDARD_DEVIATION 11.7 • n=4 Participants	24.8 mg/dL STANDARD_DEVIATION 11.4 • n=21 Participants
HDL-C Concentration	53.2 mg/dL STANDARD_DEVIATION 16.5 • n=5 Participants	49.1 mg/dL STANDARD_DEVIATION 12.7 • n=7 Participants	50.4 mg/dL STANDARD_DEVIATION 16.1 • n=5 Participants	51.9 mg/dL STANDARD_DEVIATION 16.0 • n=4 Participants	51.1 mg/dL STANDARD_DEVIATION 15.6 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in LDL-C at Week 12	-2.02 percent change Standard Error 2.49	5.53 percent change Standard Error 3.25	-61.25 percent change Standard Error 1.77	-55.74 percent change Standard Error 2.25

PRIMARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	-1.08 percent change Standard Error 2.41	2.30 percent change Standard Error 2.41	-61.23 percent change Standard Error 1.71	-63.25 percent change Standard Error 1.70

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	-6.5 mg/dL Standard Error 4.2	-1.3 mg/dL Standard Error 4.1	-101.7 mg/dL Standard Error 3.0	-98.8 mg/dL Standard Error 2.9

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Change From Baseline in LDL-C at Week 12	-8.5 mg/dL Standard Error 4.2	4.1 mg/dL Standard Error 5.2	-101.3 mg/dL Standard Error 3.0	-87.2 mg/dL Standard Error 3.6

SECONDARY outcome

Timeframe: Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)	1.9 percentage of participants Interval 0.3 to 9.9	1.9 percentage of participants Interval 0.3 to 9.8	67.0 percentage of participants Interval 57.7 to 75.1	80.4 percentage of participants Interval 71.9 to 86.8

SECONDARY outcome

Timeframe: Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12	2.0 percentage of participants Interval 0.3 to 10.3	2.2 percentage of participants Interval 0.4 to 11.3	68.3 percentage of participants Interval 58.8 to 76.4	63.1 percentage of participants Interval 53.5 to 71.8

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12	0.21 percent change Standard Error 2.29	2.72 percent change Standard Error 2.21	-55.79 percent change Standard Error 1.63	-57.28 percent change Standard Error 1.56

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12	-1.39 percent change Standard Error 2.40	5.29 percent change Standard Error 2.94	-56.19 percent change Standard Error 1.71	-49.67 percent change Standard Error 2.04

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12	-0.19 percent change Standard Error 2.10	2.21 percent change Standard Error 1.97	-49.58 percent change Standard Error 1.48	-52.76 percent change Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B at Week 12	-0.67 percent change Standard Error 2.32	4.60 percent change Standard Error 2.70	-49.75 percent change Standard Error 1.63	-44.81 percent change Standard Error 1.80

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12	0.86 percent change Standard Error 2.05	4.14 percent change Standard Error 2.13	-45.74 percent change Standard Error 1.45	-45.02 percent change Standard Error 1.50

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12	0.12 percent change Standard Error 2.19	7.11 percent change Standard Error 3.13	-45.95 percent change Standard Error 1.56	-38.32 percent change Standard Error 2.15

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12	0.78 percent change Standard Error 2.21	1.65 percent change Standard Error 2.35	-52.39 percent change Standard Error 1.56	-53.91 percent change Standard Error 1.60

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12	1.54 percent change Standard Error 2.49	4.23 percent change Standard Error 3.66	-52.74 percent change Standard Error 1.75	-45.31 percent change Standard Error 2.42

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12	7.34 percent change Standard Error 2.97	5.35 percent change Standard Error 2.95	-24.03 percent change Standard Error 2.09	-25.65 percent change Standard Error 2.07

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Lipoprotein (a) at Week 12	8.68 percent change Standard Error 3.27	6.69 percent change Standard Error 3.16	-22.89 percent change Standard Error 2.31	-21.55 percent change Standard Error 2.17

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	9.09 percent change Standard Error 3.02	7.49 percent change Standard Error 3.26	-13.27 percent change Standard Error 2.14	-9.25 percent change Standard Error 2.27

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Triglycerides at Week 12	3.50 percent change Standard Error 3.51	6.43 percent change Standard Error 4.15	-16.09 percent change Standard Error 2.49	-5.13 percent change Standard Error 2.84

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	-0.45 percent change Standard Error 1.70	-2.86 percent change Standard Error 1.84	7.93 percent change Standard Error 1.20	6.62 percent change Standard Error 1.29

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in HDL-C at Week 12	-1.15 percent change Standard Error 1.91	-3.73 percent change Standard Error 2.35	8.05 percent change Standard Error 1.35	5.35 percent change Standard Error 1.62

SECONDARY outcome

Timeframe: Baseline and Weeks 10 and 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12	8.66 percent change Standard Error 2.90	6.34 percent change Standard Error 3.27	-13.97 percent change Standard Error 2.06	-9.20 percent change Standard Error 2.27

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set

Outcome measures

Measure	Placebo Q2W n=54 Participants Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 Participants Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 Participants Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 Participants Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Percent Change From Baseline in VLDL-C at Week 12	3.73 percent change Standard Error 3.50	4.10 percent change Standard Error 4.17	-17.25 percent change Standard Error 2.48	-5.06 percent change Standard Error 2.84

Adverse Events

Placebo Q2W

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo QM

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Evolocumab Q2W

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Evolocumab QM

Serious events: 4 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Q2W n=54 participants at risk Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 participants at risk Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 participants at risk Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Cardiac disorders Acute myocardial infarction	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Angina pectoris	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Coronary artery disease	1.9% 1/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Inguinal hernia	1.9% 1/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood creatine phosphokinase increased	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Colonoscopy abnormal	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Endoscopy gastrointestinal abnormal	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Epilepsy	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Depression	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Measure	Placebo Q2W n=54 participants at risk Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.	Placebo QM n=55 participants at risk Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.	Evolocumab Q2W n=110 participants at risk Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.	Evolocumab QM n=110 participants at risk Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Infections and infestations Nasopharyngitis	3.7% 2/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 3/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.3% 8/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 11/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.4% 7/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.91% 1/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 2/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 6/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	1.9% 1/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 3/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 4/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	1.9% 1/54 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 3/55 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 4/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.5% 5/110 • From the first dose of blinded investigational product until the end of the study (up to 14 weeks). Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER