Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2

NCT01763905 | Completed Phase 3 Results DMC

• 2 other identifiers: 201101162012-001364-30
• Study Type: interventional
• Target: 307
• Locations: 14 countries
• Sites: 58

Brief Summary

The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).

Conditions

Hyperlipidemia

Keywords

High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (20)

• 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

• 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

• Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12

  Week 12

• Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

Study Arms (4)

Ezetimibe (Q2W)

ACTIVE COMPARATOR

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Drug: Placebo to Evolocumab; Drug: Ezetimibe

Ezetimibe (QM)

ACTIVE COMPARATOR

Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Drug: Placebo to Evolocumab; Drug: Ezetimibe

Evolocumab Q2W

EXPERIMENTAL

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

Biological: Evolocumab; Drug: Placebo to Ezetimibe

Evolocumab QM

EXPERIMENTAL

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

Biological: Evolocumab; Drug: Placebo to Ezetimibe

Interventions

Evolocumab BIOLOGICAL

Subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab Q2W; Evolocumab QM

Placebo to Evolocumab DRUG

Subcutaneous injection

Ezetimibe (Q2W); Ezetimibe (QM)

Ezetimibe DRUG

Tablet for oral administration

Also known as: Zetia

Ezetimibe (Q2W); Ezetimibe (QM)

Placebo to Ezetimibe DRUG

Tablet for oral administration

Evolocumab Q2W; Evolocumab QM

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 to ≤ 80 years of age
• Not on a statin or on a low dose statin with stable dose for at least 4 weeks
• History of intolerance to at least 2 statins
• Subject not at LDL-C goal
• Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
• Fasting triglycerides ≤ 400 mg/dL

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (58)

Research Site

Carmichael, California, 95608, United States

Location

Research Site

Los Angeles, California, 90048, United States

Location

Research Site

Mission Viejo, California, 92691, United States

Location

Research Site

Thousand Oaks, California, 91360, United States

Location

Research Site

Atlanta, Georgia, 30338, United States

Location

Research Site

Atlanta, Georgia, 30342, United States

Location

Research Site

Savannah, Georgia, 31406, United States

Location

Research Site

Auburn, Maine, 04210, United States

Location

Research Site

Traverse City, Michigan, 49684, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Henderson, Nevada, 89052, United States

Location

Research Site

Las Vegas, Nevada, 89117, United States

Location

Research Site

Las Vegas, Nevada, 89148, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

Raleigh, North Carolina, 27609, United States

Location

Research Site

Akron, Ohio, 44311, United States

Location

Research Site

Cincinnati, Ohio, 45212, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Norman, Oklahoma, 73069, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Camperdown, New South Wales, 2015, Australia

Location

Research Site

Milton, Queensland, 4064, Australia

Location

Research Site

Melbourne, Victoria, 3004, Australia

Location

Research Site

Perth, Western Australia, 6000, Australia

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

Ghent, 9000, Belgium

Location

Research Site

La Louvière, 7100, Belgium

Location

Research Site

Newmarket, Ontario, L3Y 5G8, Canada

Location

Research Site

Lachine, Quebec, H8S 2E4, Canada

Location

Research Site

Pointe-Claire, Quebec, H9R 3J1, Canada

Location

Research Site

Aalborg, 9000, Denmark

Location

Research Site

Ballerup Municipality, 2750, Denmark

Location

Research Site

Vejle, 7100, Denmark

Location

Research Site

Lille, 59037, France

Location

Research Site

Paris, 75651, France

Location

Research Site

Vénissieux, 69200, France

Location

Research Site

Bad Krozingen, 79189, Germany

Location

Research Site

Dresden, 01307, Germany

Location

Research Site

Heppenheim an der Bergstrasse, 64646, Germany

Location

Research Site

Hong Kong, Hong Kong

Location

Research Site

New Territories, Hong Kong

Location

Research Site

Alkmaar, 1815 JD, Netherlands

Location

Research Site

Amsterdam, 1105 AZ, Netherlands

Location

Research Site

Groningen, 9713 GZ, Netherlands

Location

Research Site

Lodz, 90-368, Poland

Location

Research Site

Warsaw, 04-730, Poland

Location

Research Site

Midrand, Gauteng, 1685, South Africa

Location

Research Site

Observatory, Western Cape, 7925, South Africa

Location

Research Site

Somerset West, Western Cape, 7130, South Africa

Location

Research Site

Córdoba, Andalusia, 14004, Spain

Location

Research Site

Zaragoza, Aragon, 50009, Spain

Location

Research Site

Reus, Catalonia, 43204, Spain

Location

Research Site

Lugano, 6900, Switzerland

Location

Research Site

Reinach, 4153, Switzerland

Location

Research Site

Liverpool, L22 0LG, United Kingdom

Location

Research Site

London, NW3 2QG, United Kingdom

Location

Research Site

Telford, TF1 6TF, United Kingdom

Location

Research Site

West Bromwich, B71 4HJ, United Kingdom

Location

Related Publications (11)

• 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.

  PMID: 28249876 BACKGROUND

• 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.

  PMID: 29736889 BACKGROUND

• Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.

  PMID: 30073585 BACKGROUND

• 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.

  PMID: 29353350 BACKGROUND

• 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.

  PMID: 29768954 BACKGROUND

• Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.

  PMID: 24477778 BACKGROUND

• Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.

  PMID: 24694531 BACKGROUND

• 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.

  PMID: 30755061 BACKGROUND

• 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.

  PMID: 30120772 BACKGROUND

• 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.

  PMID: 32114889 BACKGROUND

• 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.

  PMID: 32564340 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipidemias; Hypercholesterolemia

Interventions

evolocumab; Ezetimibe

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 9, 2013
• Study Start: January 24, 2013
• Primary Completion: November 19, 2013
• Study Completion: November 19, 2013
• Last Updated: July 20, 2020
• Results First Posted: December 22, 2015

Record last verified: 2020-07

Locations

NL (3); BE (3); ES (3); US (20); CH (2); CA (3); FR (3); GB (4); ZA (3); HK (2); AU (4); DK (3); PL (2); DE (3)