Recent Updates
Recently added Catalysts

Evolocumab

Phase 3

Hypercholesterolemia | Monoclonal antibody | Metabolic |Amgen Inc.|Last Updated: Jun 25, 2026

Target and mechanism

Molecular targetPCSK9
Target classInhibitor
ModalityMonoclonal antibody

Success Probability

Subscribe to view

Market & Valuation

Subscribe to view

Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials7
Total Enrollment4,493

FDA Designations

No designations recorded

Clinical trial landscape

Evolocumab · 37 trials · 22 indications

Phase 3 23Phase 2 11Phase 1 2Early Phase 1 1
NCT03872401Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or StrokeCoronary Heart Disease (CHD)
COMPLETED12,301 Analytics
NCT03570697Imaging of Coronary Plaques in Participants Treated With EvolocumabCoronary Artery Disease (CAD)
COMPLETED164 Analytics
NCT02833844Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed DyslipidemiaSubjects With Hyperlipidemia, Dyslipidemia and HIV Infection
COMPLETED467 Analytics
NCT02624869Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)Familial Hypercholesterolemia
COMPLETED163 Analytics
NCT02867813Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk Open-label ExtensionDyslipidemia
COMPLETED5,035 Analytics
NCT02739984Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed DyslipidemiaHypercholesterolemia
COMPLETED424 Analytics
NCT02729025Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))Subjects With Hyperlipidemia, Dyslipidemia
COMPLETED129 Analytics
NCT02662569Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed DyslipidemiaDiabetes, Hyperlipidemia, Mixed Dyslipidemia
COMPLETED986 Analytics
NCT02392559Trial Assessing Efficacy, Safety and Tolerability of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition in Paediatric Subjects With Genetic Low-Density Lipoprotein (LDL) DisordersHeterozygous Familial Hypercholesterolemia
COMPLETED158 Analytics
NCT02634580Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4Hypercholesterolemia
COMPLETED61 Analytics
PHASE3COMPLETED
Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
Coronary Heart Disease (CHD)Unlock trial analytics
PHASE3COMPLETED
Imaging of Coronary Plaques in Participants Treated With Evolocumab
Coronary Artery Disease (CAD)Unlock trial analytics
PHASE3COMPLETED
Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia
Subjects With Hyperlipidemia, Dyslipidemia and HIV InfectionUnlock trial analytics
PHASE3COMPLETED
Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
Familial HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk Open-label Extension
DyslipidemiaUnlock trial analytics
PHASE3COMPLETED
Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia
HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))
Subjects With Hyperlipidemia, DyslipidemiaUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed Dyslipidemia
Diabetes, Hyperlipidemia, Mixed DyslipidemiaUnlock trial analytics
PHASE3COMPLETED
Trial Assessing Efficacy, Safety and Tolerability of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition in Paediatric Subjects With Genetic Low-Density Lipoprotein (LDL) Disorders
Heterozygous Familial HypercholesterolemiaUnlock trial analytics
PHASE3COMPLETED
Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4
HypercholesterolemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants Who Experienced Coronary Heart Disease (CHD) Death, Myocardial Infarction (MI), or Ischemic Stroke, Whichever Occurred First
From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months

All deaths and individual components were adjudicated by an independent external clinical events committee (CEC), using standardized definitions. The number of participants who experienced CHD death, MI, or ischemic stroke, whichever occurred first, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed.

Number of Participants Who Experienced CHD Death, MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization, Whichever Occurred First
From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months

All deaths and individual components were adjudicated by an independent external CEC, using standardized definitions. The number of participants who experienced CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurred first, among participants at high cardiovascular risk without prior MI or stroke and were receiving optimized lipid lowering therapy was analyzed.

Absolute Change From Baseline in Minimum FCT
Baseline, week 50

Absolute change from baseline in minimum FCT in a matched segment of artery as determined by OCT. Minimum FCT for a participant is defined as the minimum of all minimum FCT measurements within each individual frame across all frames of that participant. Higher value of FCT indicates a better situation.

Percent Change From Baseline in LDL-C at Week 24
Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
From first dose of evolocumab in this study up to and including 30 days after the last dose or up to the end of study date, whichever was earlier; up to 80 weeks.

An adverse event is defined as any untoward medical occurrence in a clinical trial participant, not necessarily having a causal relationship with study treatment. A serious AE is as an AE that met at least 1 of the following criteria: * fatal; * life threatening; * required in-patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. AEs were graded for severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; urgent intervention indicated; Grade 5: Death related to AE.

Number of Participants Who Experienced an Adverse Event
Up to 5 years

All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.

Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Baseline and Weeks 10 and 12
Percent Change From Baseline in LDL-C at Week 12
Baseline and week 12
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
Baseline and week 16

Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics. The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.

Percent Change From Baseline to Week 24 in LDL-C
Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from interactive voice response system \[IVRS\]), scheduled visit and the interaction of treatment with scheduled visit as covariates. The model uses an unstructured covariance.

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12
Baseline and Weeks 10 and 12

For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Baseline and week 12
Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy
Week 5 and week 6

Avoidance of apheresis at end of randomized therapy was defined as no apheresis at week 5 and week 6. Aperesis at weeks 5 or 6 was based on LDL-C level at week 4: participants with LDL-C ≥ 100 mg/dL at week 4 received apheresis at week 5 (participants who received apheresis QW before study entry) or week 6 (participants who received apheresis Q2W prior to study entry). If LDL-C was \< 100 mg/dL at week 4, no apheresis was performed at week 5 or week 6, irrespective of assigned treatment group. Participants who ended the study prior to week 6 were considered as not achieving apheresis avoidance.

Number of Participants With Adverse Events
From first dose of evolocumab up to 30 days after the last dose, or end of study, whichever was earlier, up to 108 weeks.

The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe or medically significant AE, Grade 4 = Life-threatening consequences, and Grade 5 = death related to AE. An adverse device effect was defined as any adverse event related to the use of a medical device (autoinjector/pen or automated mini doser \[AMD\]), including but not limited to, AEs resulting from insufficient or inadequate Instructions for Use, AEs resulting from any malfunction of the device, or AEs resulting from use error or from intentional misuse of the device.

Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score
Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).

Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found. The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.

Percent Change From Baseline in Low-density Lipoprotein (LDL) Apolipoprotein B-100 Fractional Catabolic Rate (FCR)
Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration.

The fractional catabolic rate (the percentage of apolipoprotein B-100 in LDL which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation, and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.

Change From Baseline in Percent Atheroma Volume at Week 78
Baseline and week 78

Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma.

Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization
Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported.

All deaths and potential endpoint events were adjudicated by an independent external Clinical Events Committee (CEC) led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.

Percent Change From Baseline in LDL-C at Week 52
Baseline and Week 52

Cholesterol was measured by means of ultracentrifugation.

Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab
12 weeks

The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.

Change in LDL-Cholesterol
Baseline, 25-30 days

The difference, in the percent change in LDL-cholesterol (mg/dL), from baseline to the 25-30 day values.

Percent Change in LDL-Cholesterol
Baseline to 30 days
Change From Baseline in Target to Background Ratio Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scans
Baseline to 30 days

PET Imaging for Inflammation: Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium.

Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Baseline and Week 12

LDL-C was quantified using the ultracentrifugation method.

Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Baseline and Week 12

LDL-C was quantified using the ultracentrifugation method.

Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe
Baseline and Week 12

LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.

Maximum Observed Serum Concentration (Cmax) of Evolocumab
Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.

Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab
Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Number of Participants With Anti-Evolocumab Antibodies
From the first dose of study drug until Day 85

Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies

Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue
AAA Repair (Week 5)

IL-6 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA.

Secondary Endpoints

Number of Participants Who Experienced MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization
From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months
Number of Participants Who Experienced CHD Death, MI, or Any Ischemia-driven Arterial Revascularization
From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months
Number of Participants Who Experienced Cardiovascular Death, MI, or Ischemic Stroke
From enrollment to last confirmed survival status date; median (min, max) time on trial was 55.2 (0.0, 72.7) months
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORParticipants will receive placebo subcutaneous injection once every 2 weeks (Q2W).
Evolocumab 140 mg Q2WEXPERIMENTALParticipants will receive 140 mg evolocumab by subcutaneous injection Q2W.
EvolocumabEXPERIMENTALParticipants receive evolocumab subcutaneous injection once every month (QM) for 48 weeks. As prescribed and provided by the investigator, participants will be treated with maximally tolerated statin therapy, not expected to change for the duration of the study participation.
Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QMEXPERIMENTALDouble-blind placebo subcutaneous (SC) injection every 4 weeks (QM) for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.
Double-Blind Evolocumab 420 mg SC QM/Open-Label Evolocumab 420 mg SC QMPLACEBO_COMPARATORDouble-blind evolocumab SC injection QM for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.
evolocumab (AMG 145)EXPERIMENTALAll subjects are randomized to a single arm and will receive evolocumab 140mg every two weeks (Q2W) or 420mg monthly (QM) according to subject's preference.
Evolocumab 420 mg QMEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks.
Atorvastatin (Q2W)ACTIVE_COMPARATORParticipants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.
Atorvastatin (QM)ACTIVE_COMPARATORParticipants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.
Evolocumab Q2W + AtorvastatinEXPERIMENTALParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.
Evolocumab QM + AtorvastatinEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.
EvoMab 420 mg QMEXPERIMENTALEvolocumab subcutaneous injection QM
Ezetimibe (Q2W)ACTIVE_COMPARATORParticipants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.
Ezetimibe (QM)ACTIVE_COMPARATORParticipants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.
Evolocumab Q2WEXPERIMENTALParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.
Evolocumab QMEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.
Low Density Lipoprotein Cholesterol (LDL-C) ApheresisACTIVE_COMPARATORParticipants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for the first 6 weeks. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.
AtorvastatinACTIVE_COMPARATORParticipants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Evolocumab and AtorvastatinEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
A5 Placebo Q2WPLACEBO_COMPARATORParticipants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
A5 Placebo QMPLACEBO_COMPARATORParticipants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks.
A5 Evolocumab Q2WEXPERIMENTALParticipants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
A5 Evolocumab QMEXPERIMENTALParticipants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
A20 Placebo Q2WPLACEBO_COMPARATORParticipants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks.
A20 Placebo QMOTHERParticipants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks.
A20 Evolocumab Q2WEXPERIMENTALParticipants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
A20 Evolocumab QMEXPERIMENTALParticipants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
Standard of CareACTIVE_COMPARATORParticipants received standard of care (SOC) treatment for the first year of the study (SOC-controlled period). At week 48, participants began treatment with evolocumab at a dose of either 140 mg every 2 weeks (Q2W) or 420 mg every month (QM), based on participant choice, for approximately 2 years during the all-investigational product \[all-IP\] period.
Evolocumab + Standard of CareEXPERIMENTALParticipants received subcutaneous evolocumab plus standard of care during the first year of the study (SOC-controlled period) and for approximately 2 years during the all-IP period. Evolocumab was administered at a dose of 140 mg every 2 weeks (Q2W) or 420 mg every month (QM) based on participant choice.
Placebo Q2WPLACEBO_COMPARATORParticipants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks.
Placebo QMPLACEBO_COMPARATORParticipants received placebo subcutaneous injection once every month (QM) for up to 12 weeks.
A10 PBO Q2WPLACEBO_COMPARATORParticipants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks.
A10 PBO QMPLACEBO_COMPARATORParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
A10 EZE (Q2W)ACTIVE_COMPARATORParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks.
A10 EZE (QM)ACTIVE_COMPARATORParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
A10 EvoMab Q2WEXPERIMENTALParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A10 EvoMab QMEXPERIMENTALParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks
A80 PBO Q2WPLACEBO_COMPARATORParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A80 PBO QMPLACEBO_COMPARATORParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks.
A80 EZE (Q2W)ACTIVE_COMPARATORParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
A80 EZE (QM)ACTIVE_COMPARATORParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
A80 EvoMab Q2WEXPERIMENTALParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A80 EvoMab QMEXPERIMENTALParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
R5 PBO Q2WPLACEBO_COMPARATORParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
R5 PBO QMPLACEBO_COMPARATORParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
R5 EvoMab Q2WEXPERIMENTALParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
R5 EvoMab QMEXPERIMENTALParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
R40 PBO Q2WPLACEBO_COMPARATORParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
R40 PBO QMPLACEBO_COMPARATORParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
R40 EvoMab Q2WEXPERIMENTALParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
R40 EvoMab QMEXPERIMENTALParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
S40 PBO Q2WPLACEBO_COMPARATORParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
S40 PBO QMPLACEBO_COMPARATORParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
S40 EvoMab Q2WEXPERIMENTALParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
S40 EvoMab QMEXPERIMENTALParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
Placebo Q4WPLACEBO_COMPARATORParticipants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Evolocumab 70 mg Q2WEXPERIMENTALParticipants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 280 mg Q4WEXPERIMENTALParticipants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Q4WEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Part A: EvolocumabEXPERIMENTALParticipants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: EvolocumabEXPERIMENTALParticipants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Part B: PlaceboPLACEBO_COMPARATORParticipants received double-blind placebo subcutaneously once a month for 12 weeks.
Evolocumab + SOCEXPERIMENTALParticipants received evolocumab 420 mg once a month plus standard of care for the first year of the study (SOC-controlled period). At week 52 participants continued treatment with evolocumab 420 mg QM for another 4 years during the all-IP period.
Evolocumab 350 mgEXPERIMENTALParticipants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mgEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
EzetimibeACTIVE_COMPARATORParticipants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab + EzetimibeEXPERIMENTALParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 280 mgEXPERIMENTALParticipants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 105 mg Q2WEXPERIMENTALParticipants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 350 mg Q4WEXPERIMENTALParticipants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Interventions

NameTypeDescription
EvolocumabDRUGAdministered subcutaneously using an autoinjector pen.
PlaceboDRUGAdministered subcutaneously using an autoinjector pen.
Statin therapyDRUGhigh-intensity statin treatment with atorvastatin ≥ 40 mg daily or equivalent as background therapy Investigators will up-titrate statin therapy to the maximally tolerated dose, in accordance with local guidelines, prior to randomization.
Placebo to EvolocumabDRUGAdministered by subcutaneous injection with an automated mini doser
AtorvastatinDRUGAdministered orally once a day
EzetimibeDRUGTablet for oral administration
Placebo EzetimibeDRUGTablet for oral administration
Low-density Lipoprotein Cholesterol (LDL-C) ApheresisPROCEDUREParticipants received apheresis for LDL-C according the their physician's prescription and local custom.
Background Statin TherapyDRUGParticipants were required to be on a stable, high- to moderate-intensity statin background therapy consisting of an effective statin dose, ie, at least atorvastatin 20 mg daily or equivalent, and where locally approved, highly effective statin therapy (defined as at least atorvastatin 40 mg daily or equivalent) was recommended.
Placebo to AtorvastatinDRUGAdministered by mouth
Standard of CareDRUGStandard of care therapy as per local practices. This could include prescribed therapies and/or dietary/exercise regimes
Placebo to EzetimibeDRUGTablet for oral administration
RosuvastatinDRUGAdministered orally once a day
SimvastatinDRUGAdministered orally once a day
Diet OnlyOTHERDiet only, no lipid lowering background drug given
PlacebosDRUGMatching placebo.
Unlock Study Design Details

Eligibility Criteria

Age Range50 Years to 79 Years
SexALL
Healthy VolunteersNo
Study Sites852

Inclusion criteria: * Age: Adult participants ≥ 50 (men) or ≥ 55 (women) to ˂ 80 years of age (either sex) and meeting lipid criteria. * Lipid Criteria: Low-density lipoprotein cholesterol (LDL-C) ≥ 90 mg/dL (≥ 2.3 mmol/L) or non high-density lipoprotein cholesterol (non-HDL)-C ≥ 120 mg/dL (≥ 3.1 m...

Countries:United StatesArgentinaAustraliaAustriaBelgiumBrazilBulgariaCanadaCzechiaDenmarkEstoniaFinlandFranceGermanyGreeceHungaryIcelandItalyLatviaLithuaniaMexicoNetherlandsPolandPortugalRomaniaRussiaSlovakiaSouth KoreaSpainSwedenTaiwanUkraineUnited KingdomSouth AfricaSwitzerlandColombiaMalaysiaNorwaySloveniaTurkey (Türkiye)ChinaNew ZealandJapanChileIrelandIsraelHong KongPhilippinesSingaporeIndiaLebanon
Unlock Eligibility Criteria

Recent Changes (Last 90 Days)

MEDIUMJul 26, 2026NCT03872401TRIAL_REMOVED: changed
MEDIUMJul 26, 2026NCT03872401TRIAL_REMOVED: changed
MEDIUMJul 26, 2026NCT03872401TRIAL_REMOVED: changed
MEDIUMJun 1, 2026NCT03515304TRIAL_REMOVED: changed
MEDIUMJun 1, 2026NCT03515304TRIAL_REMOVED: changed
MEDIUMJun 1, 2026NCT03515304TRIAL_REMOVED: changed
LOWMay 24, 2026NCT03515304studyFirstPostDate: changed

Frequently asked questions about Evolocumab

What is Evolocumab used for?

Evolocumab is used for lowering low-density lipoprotein cholesterol (LDL-C) in subjects with hyperlipidemia, dyslipidemia and HIV infection, coronary heart disease (CHD), severe familial hypercholesterolemia, hyperlipidemia and mixed dyslipidemia, coronary artery disease (CAD), and familial hypercholesterolemia. It is being developed by Amgen Inc. for the cardiovascular therapeutic area.

What does Evolocumab target?

Evolocumab targets PCSK9, a protein that regulates cholesterol levels. It is a PCSK9 inhibitor, which means it blocks the action of PCSK9 to help lower LDL cholesterol. This mechanism is relevant for treating conditions like hyperlipidemia and familial hypercholesterolemia.

Who makes Evolocumab?

Evolocumab is developed by Amgen Inc., a biopharmaceutical company traded on NASDAQ under the ticker AMGN. Amgen is conducting clinical trials to evaluate the safety and efficacy of Evolocumab in patients with various lipid disorders.

What phase is Evolocumab in?

Evolocumab is in Phase 1 of clinical development, according to the latest data. It is an investigational drug and has not been approved by regulatory authorities. The drug is being studied in multiple Phase 3 trials, but the overall development phase is listed as Phase 1.

What clinical trials is Evolocumab in?

Evolocumab has been studied in several clinical trials, including NCT01953328 in Japanese patients with advanced cardiovascular risk, NCT02189837 in patients with primary hyperlipidemia and mixed dyslipidemia, NCT02624869 in children with familial hypercholesterolemia, and NCT02833844 in participants with HIV and hyperlipidemia or mixed dyslipidemia. These trials have been completed.

Is Evolocumab the same as AMG 145?

Yes, Evolocumab is also known as AMG 145. Clinical trial titles refer to Evolocumab (AMG 145), confirming that these names refer to the same drug. This alternative name is used in studies such as NCT01953328 and NCT02624869.