Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

Hypercholesterolemia Clinical Trial

— DESCARTES  

Official title:

A Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of AMG 145 (Evolocumab) on LDL-C in Hyperlipidemic Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01516879
• Other study ID #: 20110109
• Status: Completed
• Phase: Phase 3
• Start date: January 5, 2012
• Est. completion date: October 14, 2013

Study information

• Verified date: July 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.

Description:

Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:

1. no drug therapy required - diet alone

2. low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)

3. high dose drug therapy required - diet plus atorvastatin 80 mg PO QD

4. maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.

If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 905
• Est. completion date: October 14, 2013
• Est. primary completion date: October 14, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subject has provided informed consent.

• Fasting LDL-C = 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:

• < 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent

• < 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent

• OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD

• Fasting triglycerides = 400 mg/dL

Exclusion Criteria:

• New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction < 30%

• Uncontrolled cardiac arrhythmia

• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes

• Uncontrolled hypertension

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Biological:
• Evolocumab
Administered by subcutaneous injection once a month
• Placebo
Administered by subcutaneous injection once a month

Drug:
• Atorvastatin
Background lipid lowering therapy: 10 mg or 80 mg atorvastatin orally once daily.
• Ezetimibe
Background lipid lowering therapy: ezetimibe 10 mg orally once a day

Other:
• Diet Only
Diet only, no lipid lowering background drug given

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Carina Heights	Queensland
Australia	Research Site	Fitzroy	Victoria
Australia	Research Site	Maroubra	New South Wales
Australia	Research Site	Milton	Queensland
Australia	Research Site	Perth	Western Australia
Austria	Research Site	Feldkirch
Austria	Research Site	Innsbruck
Austria	Research Site	Salzburg
Austria	Research Site	Wels
Belgium	Research Site	Anthée
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Gozee
Belgium	Research Site	Ham
Belgium	Research Site	Oostende
Canada	Research Site	Bay Roberts	Newfoundland and Labrador
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Pointe-Claire	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Victoria	British Columbia
Czechia	Research Site	Brno
Czechia	Research Site	Brno
Czechia	Research Site	Chomutov
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Pardubice
Czechia	Research Site	Plzen
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
Czechia	Research Site	Slany
Denmark	Research Site	Aalborg
Denmark	Research Site	Ballerup
Denmark	Research Site	Vejle
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Komarom
Hungary	Research Site	Pecs
Hungary	Research Site	Szeged
Hungary	Research Site	Zalaegerszeg
South Africa	Research Site	Amanzimtoti	KwaZulu-Natal
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Chatsworth, Durban	KwaZulu-Natal
South Africa	Research Site	Lyttelton	Gauteng
South Africa	Research Site	Observatory	Western Cape
South Africa	Research Site	Paarl	Western Cape
South Africa	Research Site	Parow	Western Cape
South Africa	Research Site	Somerset West	Western Cape
United States	Research Site	Akron	Ohio
United States	Research Site	Anaheim	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Auburn	Maine
United States	Research Site	Bethesda	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Brockton	Massachusetts
United States	Research Site	Chevy Chase	Maryland
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	Maryland
United States	Research Site	DeLand	Florida
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Encinitas	California
United States	Research Site	Endwell	New York
United States	Research Site	Fargo	North Dakota
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New Windsor	New York
United States	Research Site	Norman	Oklahoma
United States	Research Site	Olive Branch	Mississippi
United States	Research Site	Ponte Vedra	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Renton	Washington
United States	Research Site	Richmond	Virginia
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	Savannah	Georgia
United States	Research Site	Seattle	Washington
United States	Research Site	Spring Valley	California
United States	Research Site	Westlake Village	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Hungary,  South Africa, 

References & Publications (12)

Blom DJ, Djedjos CS, Monsalvo ML, Bridges I, Wasserman SM, Scott R, Roth E. Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study. Circ Res. 2015 Sep 25;117(8):731-41. doi: 10.1161/CIRCRESAHA.115.307071. Epub 2015 Jul 30. — View Citation

Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29. — View Citation

Blom DJ, Koren MJ, Roth E, Monsalvo ML, Djedjos CS, Nelson P, Elliott M, Wasserman SM, Ballantyne CM, Holman RR. Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab. 2017 Jan;19(1):98-107. doi: 10.1111/dom.12788. Epub 2016 Oct 14. — View Citation

Daviglus ML, Ferdinand KC, López 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. — View Citation

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. Review. — View Citation

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. — View Citation

Sattar N, Toth PP, Blom DJ, Koren MJ, Soran H, Uhart M, Elliott M, Cyrille M, Somaratne R, Preiss D. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol. 2017 Nov 1;120(9):1521-1527. doi: 10.1016/j.amjcard.2017.07.047. Epub 2017 Jul 31. — View Citation

Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jun 6. pii: S1933-2874(22)00174-X. doi: 10.1016/j.jacl.2022.05.069. [Epub ahead of print] — View Citation

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. — View Citation

Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, López 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. — View Citation

Toth PP, Sattar N, Blom DJ, Martin SS, Jones SR, Monsalvo ML, Elliott M, Davis M, Somaratne R, Preiss D. Effect of Evolocumab on Lipoprotein Particles. Am J Cardiol. 2018 Feb 1;121(3):308-314. doi: 10.1016/j.amjcard.2017.10.028. Epub 2017 Nov 8. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in LDL-C at Week 52	Cholesterol was measured by means of ultracentrifugation.	Baseline and Week 52
Secondary	Change From Baseline in LDL-C at Week 52	Cholesterol was measured by means of ultracentrifugation.	Baseline and Week 52
Secondary	Percentage of Participants With an LDL-C Response at Week 52	An LDL-C response is defined as LDL-C level < 70 mg/dL (1.8 mmol/L) at Week 52.	Week 52
Secondary	Percent Change From Baseline in LDL-C at Week 12	Cholesterol was measured by means of ultracentrifugation.	Baseline and Week 12
Secondary	Percent Change From Baseline in Total Cholesterol at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Total Cholesterol at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Apolipoprotein B at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Lipoprotein(a) at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Triglycerides at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52		Baseline and Week 52
Secondary	Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52	Cholesterol was measured by means of ultracentrifugation.	Baseline and Week 52
Secondary	Percent Change From Week 12 to Week 52 in LDL-C	Cholesterol was measured by means of ultracentrifugation.	Week 12 and Week 52

External Links

•   AmgenTrials clinical trials website