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

Hyperlipidemia Clinical Trial

— GAUSS-2  

Official title:

A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01763905
• Other study ID #: 20110116
• Secondary ID: 2012-001364-30
• Status: Completed
• Phase: Phase 3
• Start date: January 24, 2013
• Est. completion date: November 19, 2013

Study information

• Verified date: July 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: November 19, 2013
• Est. primary completion date: November 19, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Biological:
• Evolocumab
Subcutaneous injection

Drug:
• Placebo to Evolocumab
Subcutaneous injection
• Ezetimibe
Tablet for oral administration
• Placebo to Ezetimibe
Tablet for oral administration

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	Milton	Queensland
Australia	Research Site	Perth	Western Australia
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Belgium	Research Site	La Louvière
Canada	Research Site	Lachine	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Pointe-Claire	Quebec
Denmark	Research Site	Aalborg
Denmark	Research Site	Ballerup
Denmark	Research Site	Vejle
France	Research Site	Lille Cedex
France	Research Site	Paris Cedex 13
France	Research Site	Vénissieux
Germany	Research Site	Bad Krozingen
Germany	Research Site	Dresden
Germany	Research Site	Heppenheim
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	New Territories
Netherlands	Research Site	Alkmaar
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Groningen
Poland	Research Site	Lodz
Poland	Research Site	Warszawa
South Africa	Research Site	Midrand	Gauteng
South Africa	Research Site	Observatory	Western Cape
South Africa	Research Site	Somerset West	Western Cape
Spain	Research Site	Cordoba	Andalucía
Spain	Research Site	Reus	Cataluña
Spain	Research Site	Zaragoza	Aragón
Switzerland	Research Site	Lugano
Switzerland	Research Site	Reinach
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	Telford
United Kingdom	Research Site	West Bromwich
United States	Research Site	Akron	Ohio
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Auburn	Maine
United States	Research Site	Carmichael	California
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Henderson	Nevada
United States	Research Site	Houston	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Mission Viejo	California
United States	Research Site	New York	New York
United States	Research Site	Norman	Oklahoma
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Savannah	Georgia
United States	Research Site	Thousand Oaks	California
United States	Research Site	Traverse City	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Hong Kong,  Netherlands,  Poland,  South Africa,  Spain,  Switzerland,  United Kingdom, 

References & Publications (11)

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. — View Citation

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. — 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

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 Jun 20. doi: 10.1007/s40119-020-00181-8. [Epub ahead of print] — 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

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. — View Citation

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. — View Citation

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. — 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

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 11 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 12		Baseline and Week 12
Primary	Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Change From Baseline in LDL-C at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Change From Baseline in LDL-C at Week 12		Baseline and Week 12
Secondary	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
Secondary	Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12		Week 12
Secondary	Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Apolipoprotein B at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Lipoprotein (a) at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Triglycerides at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12		Baseline and Week 12
Secondary	Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12		Baseline and Week 12

External Links

•   AmgenTrials clinical trials website