Trial Outcomes & Findings for Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study (NCT NCT01375751)
NCT ID: NCT01375751
Last Updated: 2022-11-15
Results Overview
LDL-C was measured using ultracentrifugation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
168 participants
Primary outcome timeframe
Baseline and Week 12
Results posted on
2022-11-15
Participant Flow
Men and women 18 to to 75 years of age, with a diagnosis of heterozygous familial hypercholesterolemia, fasting low-density lipoprotein cholesterol (LDL-C) of ≥ 100 mg/dL, and fasting triglycerides ≤ 400 mg/dL were eligible for this study. The first patient was enrolled on 02 August 2011 and the last patient was enrolled on 20 February 2012.
Randomization was stratified on the basis of screening LDL-C level (\< 130 mg/dL \[3.4 mmol/L\] or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).
Participant milestones
| Measure |
Placebo
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
56
|
56
|
56
|
|
Overall Study
Received Treatment
|
56
|
55
|
56
|
|
Overall Study
COMPLETED
|
56
|
55
|
56
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Overall Study
Other
|
0
|
1
|
0
|
Baseline Characteristics
Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
Baseline characteristics by cohort
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Total
n=167 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49.3 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
47.6 years
STANDARD_DEVIATION 13.6 • n=7 Participants
|
51.8 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
49.6 years
STANDARD_DEVIATION 12.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
78 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
89 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
54 participants
n=5 Participants
|
55 participants
n=7 Participants
|
56 participants
n=5 Participants
|
165 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
48 participants
n=5 Participants
|
48 participants
n=7 Participants
|
52 participants
n=5 Participants
|
148 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Stratification Factor: LDL-C Level
< 130 mg/dL
|
19 participants
n=5 Participants
|
17 participants
n=7 Participants
|
19 participants
n=5 Participants
|
55 participants
n=4 Participants
|
|
Stratification Factor: LDL-C Level
≥ 130 mg/dL
|
37 participants
n=5 Participants
|
38 participants
n=7 Participants
|
37 participants
n=5 Participants
|
112 participants
n=4 Participants
|
|
Stratification Factor: Baseline Use Of Ezetimibe
No
|
20 participants
n=5 Participants
|
19 participants
n=7 Participants
|
20 participants
n=5 Participants
|
59 participants
n=4 Participants
|
|
Stratification Factor: Baseline Use Of Ezetimibe
Yes
|
36 participants
n=5 Participants
|
36 participants
n=7 Participants
|
36 participants
n=5 Participants
|
108 participants
n=4 Participants
|
|
LDL-C Concentration
|
160.8 mg/dL
STANDARD_DEVIATION 44.0 • n=5 Participants
|
156.8 mg/dL
STANDARD_DEVIATION 46.1 • n=7 Participants
|
149.5 mg/dL
STANDARD_DEVIATION 36.3 • n=5 Participants
|
155.7 mg/dL
STANDARD_DEVIATION 42.3 • n=4 Participants
|
|
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration
|
182.7 mg/dL
STANDARD_DEVIATION 52.6 • n=5 Participants
|
178.0 mg/dL
STANDARD_DEVIATION 51.7 • n=7 Participants
|
171.0 mg/dL
STANDARD_DEVIATION 43.6 • n=5 Participants
|
177.2 mg/dL
STANDARD_DEVIATION 49.4 • n=4 Participants
|
|
Apolipoprotein B Concentration
|
125.2 mg/dL
STANDARD_DEVIATION 30.3 • n=5 Participants
|
120.9 mg/dL
STANDARD_DEVIATION 29.3 • n=7 Participants
|
119.3 mg/dL
STANDARD_DEVIATION 27.6 • n=5 Participants
|
121.8 mg/dL
STANDARD_DEVIATION 29.0 • n=4 Participants
|
|
Total Cholesterol/HDL-C Ratio
|
4.895 ratio
STANDARD_DEVIATION 1.790 • n=5 Participants
|
5.119 ratio
STANDARD_DEVIATION 1.923 • n=7 Participants
|
4.857 ratio
STANDARD_DEVIATION 1.688 • n=5 Participants
|
4.956 ratio
STANDARD_DEVIATION 1.795 • n=4 Participants
|
|
Apolipoprotein B/Apolipoprotein A1 Ratio
|
0.899 ratio
STANDARD_DEVIATION 0.277 • n=5 Participants
|
0.901 ratio
STANDARD_DEVIATION 0.286 • n=7 Participants
|
0.867 ratio
STANDARD_DEVIATION 0.264 • n=5 Participants
|
0.899 ratio
STANDARD_DEVIATION 0.274 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; Missing ultracentrifugation (UC) LDL-C data at Week 12 were imputed using last observation carried forward (LOCF) and calculated LDL-C.
LDL-C was measured using ultracentrifugation.
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
|
1.12 percent change
Standard Error 2.88
|
-42.70 percent change
Standard Error 2.93
|
-55.24 percent change
Standard Error 2.88
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; LOCF imputation was used.
LDL-C was measured using ultracentrifugation.
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Absolute Change From Baseline in LDL-C at Week 12
|
4.2 mg/dL
Standard Error 5.2
|
-61.3 mg/dL
Standard Error 5.4
|
-80.5 mg/dL
Standard Error 5.2
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; LOCF imputation was used.
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12
|
2.48 percent change
Standard Error 2.80
|
-39.31 percent change
Standard Error 2.86
|
-50.98 percent change
Standard Error 2.80
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; LOCF imputation was used
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B at Week 12
|
2.86 percent change
Standard Error 2.61
|
-31.89 percent change
Standard Error 2.66
|
-43.34 percent change
Standard Error 2.61
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; LOCF imputaton was used.
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
|
2.98 percent change
Standard Error 2.73
|
-33.69 percent change
Standard Error 2.79
|
-42.03 percent change
Standard Error 2.73
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Full analysis set; LOCF imputation was used.
Outcome measures
| Measure |
Placebo
n=56 Participants
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 Participants
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 Participants
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12
|
-4.10 percent change
Standard Error 2.53
|
-38.02 percent change
Standard Error 2.58
|
-48.74 percent change
Standard Error 2.53
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Evolocumab 350 mg
Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths
Evolocumab 420 mg
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=56 participants at risk
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 participants at risk
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 participants at risk
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
Other adverse events
| Measure |
Placebo
n=56 participants at risk
Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 350 mg
n=55 participants at risk
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
Evolocumab 420 mg
n=56 participants at risk
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.4%
3/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.6%
2/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Nausea
|
5.4%
3/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Injection site pain
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
9.1%
5/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.6%
2/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Influenza
|
10.7%
6/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
7.1%
4/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Nasopharyngitis
|
10.7%
6/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
12.7%
7/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
12.5%
7/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Sinusitis
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
5.5%
3/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
5.5%
3/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.6%
2/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.4%
3/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Headache
|
8.9%
5/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
5.5%
3/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
5.4%
3/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.4%
3/56 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
1.8%
1/55 • 12 weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/56 • 12 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