Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01763827




Registration number
NCT01763827
Ethics application status
Date submitted
7/01/2013
Date registered
9/01/2013
Date last updated
8/11/2022

Titles & IDs
Public title
Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2
Scientific title
A Double-blind, Randomized, Placebo and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With AMG 145 in Subjects With a 10-Year Framingham Risk Score of 10% or Less
Secondary ID [1] 0 0
20110114
Universal Trial Number (UTN)
Trial acronym
MENDEL-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperlipidemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Evolocumab
Treatment: Drugs - Ezetimibe
Treatment: Other - Placebo to Evolocumab
Other interventions - Placebo to Ezetimibe

Placebo comparator: Placebo Q2W - Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.

Placebo comparator: Placebo QM - Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

Active comparator: Ezetimibe (Q2W) - Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Active comparator: Ezetimibe (QM) - Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Experimental: Evolocumab Q2W - Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Experimental: Evolocumab QM - Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.


Treatment: Other: Evolocumab
Administered by subcutaneous injection

Treatment: Drugs: Ezetimibe
Administered orally once a day

Treatment: Other: Placebo to Evolocumab
Administered by subcutaneous injection

Other interventions: Placebo to Ezetimibe
Administered orally once daily
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
Timepoint [1] 0 0
Baseline and Week 12
Primary outcome [2] 0 0
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Timepoint [2] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [1] 0 0
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Timepoint [1] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [2] 0 0
Change From Baseline in LDL-C at Week 12
Timepoint [2] 0 0
Baseline and Week 12
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Timepoint [3] 0 0
Weeks 10 and 12
Secondary outcome [4] 0 0
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Timepoint [5] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [6] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Timepoint [7] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [8] 0 0
Percent Change From Baseline in Apolipoprotein B at Week 12
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
Timepoint [9] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [10] 0 0
Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
Timepoint [10] 0 0
Baseline and Week 12
Secondary outcome [11] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Timepoint [11] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [12] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Timepoint [12] 0 0
Baseline and Week 12
Secondary outcome [13] 0 0
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Timepoint [13] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [14] 0 0
Percent Change From Baseline in Lipoprotein (a) at Week 12
Timepoint [14] 0 0
Baseline and Week 12
Secondary outcome [15] 0 0
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Timepoint [15] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [16] 0 0
Percent Change From Baseline in Triglycerides at Week 12
Timepoint [16] 0 0
Baseline and Week 12
Secondary outcome [17] 0 0
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Timepoint [17] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [18] 0 0
Percent Change From Baseline in VLDL-C at Week 12
Timepoint [18] 0 0
Baseline and Week 12
Secondary outcome [19] 0 0
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Timepoint [19] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [20] 0 0
Percent Change From Baseline in HDL-C at Week 12
Timepoint [20] 0 0
Baseline and Week 12

Eligibility
Key inclusion criteria
* Male or female = 18 to = 80 years of age
* National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less
* Fasting LDL-C = 100 mg/dL (2.6 mmol/L) and <190 mg/dL
* Fasting triglycerides = 400 mg/dL (4.5 mmol/L)
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of coronary heart disease
* New York Heart Association (NYHA) III or IV heart failure
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension
* Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)
* Uncontrolled hypothyroidism or hyperthyroidism

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/10/2013
Sample size
Target
Accrual to date
Final
615
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - Maroubra
Recruitment hospital [3] 0 0
Research Site - Carina Heights
Recruitment hospital [4] 0 0
Research Site - Sherwood
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2035 - Maroubra
Recruitment postcode(s) [3] 0 0
4152 - Carina Heights
Recruitment postcode(s) [4] 0 0
4075 - Sherwood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
North Dakota
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
South Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
South Dakota
Country [24] 0 0
United States of America
State/province [24] 0 0
Tennessee
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Utah
Country [27] 0 0
United States of America
State/province [27] 0 0
Virginia
Country [28] 0 0
United States of America
State/province [28] 0 0
Washington
Country [29] 0 0
Belgium
State/province [29] 0 0
Anthée
Country [30] 0 0
Belgium
State/province [30] 0 0
Bruxelles
Country [31] 0 0
Belgium
State/province [31] 0 0
Gozee
Country [32] 0 0
Belgium
State/province [32] 0 0
Gribomont
Country [33] 0 0
Belgium
State/province [33] 0 0
Halen
Country [34] 0 0
Belgium
State/province [34] 0 0
Ham
Country [35] 0 0
Belgium
State/province [35] 0 0
Linkebeek
Country [36] 0 0
Belgium
State/province [36] 0 0
Retie
Country [37] 0 0
Belgium
State/province [37] 0 0
Tessenderlo
Country [38] 0 0
Canada
State/province [38] 0 0
Newfoundland and Labrador
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Denmark
State/province [41] 0 0
Aalborg
Country [42] 0 0
Denmark
State/province [42] 0 0
Ballerup
Country [43] 0 0
Denmark
State/province [43] 0 0
Vejle
Country [44] 0 0
France
State/province [44] 0 0
Gières
Country [45] 0 0
France
State/province [45] 0 0
Grenoble Cedex 9
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Seoul
Country [47] 0 0
South Africa
State/province [47] 0 0
Gauteng
Country [48] 0 0
South Africa
State/province [48] 0 0
Western Cape
Country [49] 0 0
South Africa
State/province [49] 0 0
Bloemfontein
Country [50] 0 0
Taiwan
State/province [50] 0 0
Kaohsiung
Country [51] 0 0
Taiwan
State/province [51] 0 0
Taipei
Country [52] 0 0
Turkey
State/province [52] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.
Trial website
https://clinicaltrials.gov/study/NCT01763827
Trial related presentations / publications
Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H; MENDEL-2 Investigators. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2531-2540. doi: 10.1016/j.jacc.2014.03.018. Epub 2014 Mar 29.
Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.
Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.
Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01763827