Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed Dyslipidemia (BERSON)

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab (AMG 145) in Combination With Statin Therapy in Diabetic Subjects With Hyperlipidemia or Mixed Dyslipidemia (BERSON)

The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) in combination with statin therapy (atorvastatin) on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in diabetic adults with hyperlipidemia or mixed dyslipidemia.

Study Overview

• Status: Completed
• Conditions: Diabetes, Hyperlipidemia, Mixed Dyslipidemia
• Intervention / Treatment: Biological: Evolocumab; Drug: Atorvastatin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 986
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425ACG
    • Research Site
  • Córdoba, Argentina, X5003DCE
    • Research Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1405BUB
      • Research Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1012AAR
      • Research Site
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • Research Site
• Brazil
  • Rio De Janeiro, Brazil, 22271-100
    • Research Site
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil, 71625-009
      • Research Site
  • Goiás
    • Goiania, Goiás, Brazil, 74223-130
      • Research Site
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01244-030
      • Research Site
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Research Site
    • London, Ontario, Canada, N5W 6A2
      • Research Site
    • Woodstock, Ontario, Canada, N4S 5P5
      • Research Site
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Research Site
    • Montreal, Quebec, Canada, H2W 1R7
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Research Site
    • St Jean sur Richelieu, Quebec, Canada, J3A 1C3
      • Research Site
• China
  • Beijing, China, 100730
    • Research Site
  • Beijing, China, 100037
    • Research Site
  • Beijing, China, 100029
    • Research Site
  • Shanghai, China, 200080
    • Research Site
  • Shanghai, China, 200040
    • Research Site
  • Shanghai, China, 200120
    • Research Site
  • Shanghai, China, 200003
    • Research Site
  • Beijing
    • Beijing, Beijing, China, 100853
      • Research Site
  • Chongqing
    • Chongqing, Chongqing, China, 404000
      • Research Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Research Site
    • Guangzhou, Guangdong, China, 510515
      • Research Site
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Research Site
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Research Site
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • Research Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Research Site
    • Wuhan, Hubei, China, 430014
      • Research Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • Research Site
    • Changsha, Hunan, China, 410013
      • Research Site
    • Changsha, Hunan, China, 410004
      • Research Site
    • Hengyang, Hunan, China, 421001
      • Research Site
    • Zhuzhou, Hunan, China, 412000
      • Research Site
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Research Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Research Site
    • Nanjing, Jiangsu, China, 210008
      • Research Site
    • Nanjing, Jiangsu, China, 210011
      • Research Site
    • Nanjing, Jiangsu, China, 210012
      • Research Site
    • Suzhou, Jiangsu, China, 215021
      • Research Site
    • Wuxi, Jiangsu, China, 214023
      • Research Site
    • Xuzhou, Jiangsu, China, 221006
      • Research Site
    • Zhenjiang, Jiangsu, China, 212001
      • Research Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Research Site
  • Jilin
    • ChangChun, Jilin, China, 130041
      • Research Site
    • Changchun, Jilin, China, 130021
      • Research Site
    • Changchun, Jilin, China, 130033
      • Research Site
    • Siping, Jilin, China, 136000
      • Research Site
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Research Site
  • Shaanxi
    • XI An, Shaanxi, China, 710061
      • Research Site
  • Shandong
    • Jinan, Shandong, China, 250013
      • Research Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Research Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Research Site
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Research Site
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • Research Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Research Site
    • Hangzhou, Zhejiang, China, 310013
      • Research Site
    • Hangzhou, Zhejiang, China, 310014
      • Research Site
    • Linhai, Zhejiang, China, 318000
      • Research Site
    • Wenzhou, Zhejiang, China, 325000
      • Research Site
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050012
      • Research Site
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 08001000
      • Research Site
    • Barranquilla, Atlántico, Colombia, 080020
      • Research Site
    • Barranquilla, Atlántico, Colombia
      • Research Site
  • Nariño
    • Pasto, Nariño, Colombia
      • Research Site
• France
  • Dijon, France, 21079
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
  • Toulouse Cedex 9, France, 31059
    • Research Site
• Korea, Republic of
  • Bucheon-si, Wonmi-gu, Korea, Republic of, 420-717
    • Research Site
  • Busan, Korea, Republic of, 602-715
    • Research Site
  • Busan, Korea, Republic of, 602-739
    • Research Site
  • Daegu, Korea, Republic of, 705-718
    • Research Site
  • Seongnam-si, Korea, Republic of, 463-707
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 139-711
    • Research Site
  • Seoul, Korea, Republic of, 07061
    • Research Site
  • Seoul, Korea, Republic of, 137-701
    • Research Site
  • Seoul, Korea, Republic of, 110-744
    • Research Site
  • Seoul, Korea, Republic of, 152-703
    • Research Site
  • Seoul, Korea, Republic of, 130-872
    • Research Site
  • Seoul, Korea, Republic of, 110-746
    • Research Site
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Research Site
  • Moscow, Russian Federation, 121552
    • Research Site
  • Moscow, Russian Federation, 117292
    • Research Site
  • Saint-Petersburg, Russian Federation, 197022
    • Research Site
  • Saint-Petersburg, Russian Federation, 199106
    • Research Site
  • Saint-Petersburg, Russian Federation, 196601
    • Research Site
  • Saint-Petersburg, Russian Federation, 192289
    • Research Site
  • Saratov, Russian Federation, 410054
    • Research Site
  • Tomsk, Russian Federation, 634012
    • Research Site
• Turkey
  • Antalya, Turkey, 07058
    • Research Site
  • Istanbul, Turkey, 34096
    • Research Site
  • Istanbul, Turkey, 34720
    • Research Site
  • Izmir, Turkey, 35000
    • Research Site
  • Kocaeli, Turkey, 41380
    • Research Site
• United States
  • Florida
    • Miami, Florida, United States, 33173
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Research Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Research Site
    • Dayton, Ohio, United States, 45414
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females with type 2 diabetes (receiving pharmacologic treatment for at least 6 months or longer) with stable diabetes therapy
• Lipid-lowering therapy must be unchanged for at least 4 weeks or more
• Subjects receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 100 mg/dL
• Subjects not receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 130 mg/dL

Exclusion criteria:

• New York Heart Association (NYHA) class III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Type 1 diabetes or poorly controlled type 2 diabetes
• Uncontrolled hypothyroidism or hyperthyroidism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin (Q2W); Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Drug: Atorvastatin; Administered orally once a day; Other Names: Lipitor; Other: Placebo; Placebo to evolocumab administered by subcutaneous injection
Active Comparator: Atorvastatin (QM); Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks.	Drug: Atorvastatin; Administered orally once a day; Other Names: Lipitor; Other: Placebo; Placebo to evolocumab administered by subcutaneous injection
Experimental: Evolocumab Q2W + Atorvastatin; Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145; Drug: Atorvastatin; Administered orally once a day; Other Names: Lipitor
Experimental: Evolocumab QM + Atorvastatin; Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145; Drug: Atorvastatin; Administered orally once a day; Other Names: Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in LDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)	Weeks 10 and 12
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Change From Baseline in LDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12	Baseline and week 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12	Baseline and week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12	Baseline and week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B100 at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B100 at Week 12	Baseline and week 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12	Baseline and week 12
Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at Week 12	Baseline and week 12
Percentage of Participants With LDL-C Less Than 70 mg/dL (1.8 mmol/L) at Week 12	Week 12

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Blom DJ, Chen J, Yuan Z, Borges JLC, Monsalvo ML, Wang N, Hamer AW, Ge J. Effects of evolocumab therapy and low LDL-C levels on vitamin E and steroid hormones in Chinese and global patients with type 2 diabetes. Endocrinol Diabetes Metab. 2020 Mar 6;3(2):e00123. doi: 10.1002/edm2.123. eCollection 2020 Apr.
• Chen Y, Yuan Z, Lu J, Eliaschewitz FG, Lorenzatti AJ, Monsalvo ML, Wang N, Hamer AW, Ge J. Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial. Diabetes Obes Metab. 2019 Jun;21(6):1464-1473. doi: 10.1111/dom.13700. Epub 2019 Apr 14.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2016
• Primary Completion (Actual): December 6, 2017
• Study Completion (Actual): December 6, 2017

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 20, 2016
• First Posted (Estimate): January 25, 2016

Study Record Updates

• Last Update Posted (Actual): January 11, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Evolocumab
• Other Study ID Numbers: 20120119; 2013-000723-14 (EudraCT Number)