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

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

The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Ezetimibe; Biological: Evolocumab; Other: Placebo to Evolocumab

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2015
      • Research Site
    • Sydney, New South Wales, Australia, 2022
      • Research Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Research Site
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Uccle, Belgium, 1180
    • Research Site
• Canada
  • Newfoundland and Labrador
    • Saint John’s, Newfoundland and Labrador, Canada, A1A 3R5
      • Research Site
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
      • Research Site
  • Quebec
    • Lachine, Quebec, Canada, H8S 2E4
      • Research Site
• Denmark
  • Ballerup, Denmark, 2750
    • Research Site
  • Vejle, Denmark, 7100
    • Research Site
• Finland
  • Helsinki, Finland, 00029
    • Research Site
  • OYS, Finland, 90029
    • Research Site
• Spain
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
      • Research Site
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Research Site
    • Reus, Cataluña, Spain, 43204
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Research Site
    • Reus, Cataluña, Spain, 43204
      • Research Site
• Sweden
  • Göteborg, Sweden, 411 36
    • Research Site
  • Göteborg, Sweden, 411 36
    • Research Site
  • Lund, Sweden, 222 21
    • Research Site
  • Stockholm, Sweden, 141 86
    • Research Site
  • Stockholm, Sweden, 111 35
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Mission Viejo, California, United States, 92691
      • Research Site
    • Westlake Village, California, United States, 91361
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Research Site
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Savannah, Georgia, United States, 31406
      • Research Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Research Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Research Site
  • Montana
    • Butte, Montana, United States, 59701
      • Research Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Research Site
    • Las Vegas, Nevada, United States, 89117
      • Research Site
  • New York
    • New York, New York, United States, 10029
      • Research Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Research Site
  • Ohio
    • Akron, Ohio, United States, 44311
      • Research Site
    • Cincinnati, Ohio, United States, 45212
      • Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female ≥ 18 to ≤ 75 years of age
• On a statin or a low dose statin with stable dose for at least 4 weeks
• Lipid lowering therapy has been stable prior to enrollment
• Fasting triglycerides must be < 400 mg/dL.
• Subject not at LDL-C goal

Exclusion Criteria:

• New York Heart Association (NYHA) III or IV heart failure or 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 or newly diagnosed type 2 diabetes (HbA1c > 8.5%)
• Uncontrolled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ezetimibe; Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.	Drug: Ezetimibe; Administered orally once a day; Other Names: Zetia; Other: Placebo to Evolocumab; Administered by subcutaneous injection
EXPERIMENTAL: Evolocumab + Ezetimibe; Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.	Drug: Ezetimibe; Administered orally once a day; Other Names: Zetia; Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145
EXPERIMENTAL: Evolocumab 280 mg; Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145
EXPERIMENTAL: Evolocumab 350 mg; Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145
EXPERIMENTAL: Evolocumab 420 mg; Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection; Other Names: Repatha; AMG 145

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	LDL-C was measured using ultracentrifugation. Least squares (LS) means are based off an analysis of covariance (ANCOVA) model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in LDL-C at Week 12	LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Non-HDL-C at Week 12	LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12	LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12	LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12	LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.	Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe	LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, Wasserman SM, Stein EA. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012 Dec 19;308(23):2497-506. doi: 10.1001/jama.2012.25790.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 28, 2011
• Primary Completion (ACTUAL): May 8, 2012
• Study Completion (ACTUAL): May 8, 2012

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 16, 2011
• First Posted (ESTIMATE): June 17, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Cholesterol; Elevated Cholesterol; Hypercholesterolemia; High Cholesterol; Raised Cholesterol; Statin intolerant; Proprotein convertase subtilisin/kexin type 9 (PCSK9)
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antibodies, Monoclonal; Evolocumab; Ezetimibe
• Other Study ID Numbers: 20090159