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Phase 3 N=331 Randomized Quadruple-blind Treatment

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

Hyperlipidemia

Enrolled (actual)
331
Serious AEs
3.7%
Results posted
Dec 2015
Primary outcome: Primary: Percent Change From Baseline in LDL-C at Week 12 — -2.02; 5.53; -61.25; -55.74 percent change — p=<0.001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Evolocumab (Biological); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Amgen
Primary completion
Nov 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Percent Change From Baseline in LDL-C at Week 12
-2.02; 5.53; -61.25; -55.74 <0.001 sig
PRIMARY
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
-1.08; 2.30; -61.23; -63.25 <0.001 sig
SECONDARY
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
-6.5; -1.3; -101.7; -98.8 <0.001 sig
SECONDARY
Change From Baseline in LDL-C at Week 12
-8.5; 4.1; -101.3; -87.2 <0.001 sig
SECONDARY
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
1.9; 1.9; 67.0; 80.4 <0.001 sig
SECONDARY
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
2.0; 2.2; 68.3; 63.1 <0.001 sig
SECONDARY
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
0.21; 2.72; -55.79; -57.28 <0.001 sig
SECONDARY
Percent Change From Baseline in Non-HDL-C at Week 12
-1.39; 5.29; -56.19; -49.67 <0.001 sig
SECONDARY
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
-0.19; 2.21; -49.58; -52.76 <0.001 sig
SECONDARY
Percent Change From Baseline in Apolipoprotein B at Week 12
-0.67; 4.60; -49.75; -44.81 <0.001 sig
SECONDARY
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
0.86; 4.14; -45.74; -45.02 <0.001 sig
SECONDARY
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
0.12; 7.11; -45.95; -38.32 <0.001 sig
SECONDARY
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
0.78; 1.65; -52.39; -53.91 <0.001 sig
SECONDARY
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
1.54; 4.23; -52.74; -45.31 <0.001 sig
SECONDARY
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
7.34; 5.35; -24.03; -25.65 <0.001 sig
SECONDARY
Percent Change From Baseline in Lipoprotein (a) at Week 12
8.68; 6.69; -22.89; -21.55 <0.001 sig
SECONDARY
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
9.09; 7.49; -13.27; -9.25 <0.001 sig
SECONDARY
Percent Change From Baseline in Triglycerides at Week 12
3.50; 6.43; -16.09; -5.13 <0.001 sig
SECONDARY
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
-0.45; -2.86; 7.93; 6.62 <0.001 sig
SECONDARY
Percent Change From Baseline in HDL-C at Week 12
-1.15; -3.73; 8.05; 5.35 <0.001 sig
SECONDARY
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
8.66; 6.34; -13.97; -9.20 <0.001 sig
SECONDARY
Percent Change From Baseline in VLDL-C at Week 12
3.73; 4.10; -17.25; -5.06 <0.001 sig

Summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

Eligibility Criteria

Inclusion Criteria

  • Male or female ≥ 18 to ≤ 80 years of age
  • Diagnosis of heterozygous familial hypercholesterolemia
  • On a stable dose of an approved statin and lipid regulating medication
  • Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L)
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria

  • Homozygous familial hypercholesterolemia
  • LDL or plasma apheresis
  • New York Heart Association (NYHA) III or IV heart failure
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Type 1 diabetes, poorly controlled type 2 diabetes
  • Uncontrolled hypothyroidism or hyperthyroidism
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01763918). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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