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

Primary Purpose

Hyperlipidemia

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Evolocumab

Placebo to Evolocumab

Ezetimibe

Placebo to Ezetimibe

About this trial

This is an interventional treatment trial for Hyperlipidemia focused on measuring High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Ezetimibe (Q2W)

Ezetimibe (QM)

Evolocumab Q2W

Evolocumab QM

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Percent Change From Baseline in LDL-C at Week 12

Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Secondary Outcome Measures

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Change From Baseline in LDL-C at Week 12

Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)

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

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

Percent Change From Baseline in Non-HDL-C at Week 12

Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12

Percent Change From Baseline in Apolipoprotein B at Week 12

Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12

Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12

Percent Change From Baseline in Lipoprotein (a) at Week 12

Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12

Percent Change From Baseline in Triglycerides at Week 12

Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12

Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12

Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12

Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12

Full Information

NCT ID

NCT01763905

First Posted

January 7, 2013

Last Updated

July 1, 2020

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT01763905

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

January 24, 2013 (Actual)

Primary Completion Date

November 19, 2013 (Actual)

Study Completion Date

November 19, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperlipidemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

307 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ezetimibe (Q2W)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Ezetimibe (QM)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Evolocumab Q2W

Arm Type

Experimental

Arm Description

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

Arm Title

Evolocumab QM

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Evolocumab

Other Intervention Name(s)

AMG 145, Repatha

Intervention Description

Subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Placebo to Evolocumab

Intervention Description

Subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Ezetimibe

Other Intervention Name(s)

Zetia

Intervention Description

Tablet for oral administration

Intervention Type

Drug

Intervention Name(s)

Placebo to Ezetimibe

Intervention Description

Tablet for oral administration

Primary Outcome Measure Information:

Title

Percent Change From Baseline in LDL-C at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Secondary Outcome Measure Information:

Title

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Change From Baseline in LDL-C at Week 12

Time Frame

Baseline and Week 12

Title

Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)

Time Frame

Weeks 10 and 12

Title

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

Time Frame

Week 12

Title

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

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Non-HDL-C at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Apolipoprotein B at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Lipoprotein (a) at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Triglycerides at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12

Time Frame

Baseline and Week 12

Title

Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12

Time Frame

Baseline and Weeks 10 and 12

Title

Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12

Time Frame

Baseline and Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Carmichael

State/Province

California

ZIP/Postal Code

95608

Country

United States

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Facility Name

Research Site

City

Mission Viejo

State/Province

California

ZIP/Postal Code

92691

Country

United States

Facility Name

Research Site

City

Thousand Oaks

State/Province

California

ZIP/Postal Code

91360

Country

United States

Facility Name

Research Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30338

Country

United States

Facility Name

Research Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Research Site

City

Savannah

State/Province

Georgia

ZIP/Postal Code

31406

Country

United States

Facility Name

Research Site

City

Auburn

State/Province

Maine

ZIP/Postal Code

04210

Country

United States

Facility Name

Research Site

City

Traverse City

State/Province

Michigan

ZIP/Postal Code

49684

Country

United States

Facility Name

Research Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Research Site

City

Henderson

State/Province

Nevada

ZIP/Postal Code

89052

Country

United States

Facility Name

Research Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89117

Country

United States

Facility Name

Research Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89148

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Research Site

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27609

Country

United States

Facility Name

Research Site

City

Akron

State/Province

Ohio

ZIP/Postal Code

44311

Country

United States

Facility Name

Research Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45212

Country

United States

Facility Name

Research Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Research Site

City

Norman

State/Province

Oklahoma

ZIP/Postal Code

73069

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Research Site

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2015

Country

Australia

Facility Name

Research Site

City

Milton

State/Province

Queensland

ZIP/Postal Code

4064

Country

Australia

Facility Name

Research Site

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

Facility Name

Research Site

City

Perth

State/Province

Western Australia

ZIP/Postal Code

6000

Country

Australia

Facility Name

Research Site

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Research Site

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Research Site

City

La Louvière

ZIP/Postal Code

7100

Country

Belgium

Facility Name

Research Site

City

Newmarket

State/Province

Ontario

ZIP/Postal Code

L3Y 5G8

Country

Canada

Facility Name

Research Site

City

Lachine

State/Province

Quebec

ZIP/Postal Code

H8S 2E4

Country

Canada

Facility Name

Research Site

City

Pointe-Claire

State/Province

Quebec

ZIP/Postal Code

H9R 3J1

Country

Canada

Facility Name

Research Site

City

Aalborg

ZIP/Postal Code

9000

Country

Denmark

Facility Name

Research Site

City

Ballerup

ZIP/Postal Code

2750

Country

Denmark

Facility Name

Research Site

City

Vejle

ZIP/Postal Code

7100

Country

Denmark

Facility Name

Research Site

City

Lille Cedex

ZIP/Postal Code

59037

Country

France

Facility Name

Research Site

City

Paris Cedex 13

ZIP/Postal Code

75651

Country

France

Facility Name

Research Site

City

Vénissieux

ZIP/Postal Code

69200

Country

France

Facility Name

Research Site

City

Bad Krozingen

ZIP/Postal Code

79189

Country

Germany

Facility Name

Research Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Research Site

City

Heppenheim

ZIP/Postal Code

64646

Country

Germany

Facility Name

Research Site

City

Hong Kong

Country

Hong Kong

Facility Name

Research Site

City

New Territories

Country

Hong Kong

Facility Name

Research Site

City

Alkmaar

ZIP/Postal Code

1815 JD

Country

Netherlands

Facility Name

Research Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Research Site

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Research Site

City

Lodz

ZIP/Postal Code

90-368

Country

Poland

Facility Name

Research Site

City

Warszawa

ZIP/Postal Code

04-730

Country

Poland

Facility Name

Research Site

City

Midrand

State/Province

Gauteng

ZIP/Postal Code

1685

Country

South Africa

Facility Name

Research Site

City

Observatory

State/Province

Western Cape

ZIP/Postal Code

7925

Country

South Africa

Facility Name

Research Site

City

Somerset West

State/Province

Western Cape

ZIP/Postal Code

7130

Country

South Africa

Facility Name

Research Site

City

Cordoba

State/Province

Andalucía

ZIP/Postal Code

14004

Country

Spain

Facility Name

Research Site

City

Zaragoza

State/Province

Aragón

ZIP/Postal Code

50009

Country

Spain

Facility Name

Research Site

City

Reus

State/Province

Cataluña

ZIP/Postal Code

43204

Country

Spain

Facility Name

Research Site

City

Lugano

ZIP/Postal Code

6900

Country

Switzerland

Facility Name

Research Site

City

Reinach

ZIP/Postal Code

4153

Country

Switzerland

Facility Name

Research Site

City

Liverpool

ZIP/Postal Code

L22 0LG

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Facility Name

Research Site

City

Telford

ZIP/Postal Code

TF1 6TF

Country

United Kingdom

Facility Name

Research Site

City

West Bromwich

ZIP/Postal Code

B71 4HJ

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

28249876

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.

Results Reference

background

PubMed Identifier

29736889

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.

Results Reference

background

PubMed Identifier

30073585

Citation

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.

Results Reference

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PubMed Identifier

29353350

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.

Results Reference

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PubMed Identifier

29768954

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.

Results Reference

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PubMed Identifier

24477778

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.

Results Reference

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PubMed Identifier

24694531

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.

Results Reference

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PubMed Identifier

30755061

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.

Results Reference

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PubMed Identifier

30120772

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.

Results Reference

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PubMed Identifier

32114889

Citation

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.

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PubMed Identifier

32564340

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 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.

Results Reference

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Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

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

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

Hyperlipidemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial