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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01763905




Registration number
NCT01763905
Ethics application status
Date submitted
7/01/2013
Date registered
9/01/2013
Date last updated
20/07/2020

Titles & IDs
Public title
Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2
Scientific 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
Secondary ID [1] 0 0
2012-001364-30
Secondary ID [2] 0 0
20110116
Universal Trial Number (UTN)
Trial acronym
GAUSS-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperlipidemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Evolocumab
Treatment: Drugs - Placebo to Evolocumab
Treatment: Drugs - Ezetimibe
Treatment: Drugs - Placebo to Ezetimibe

Active Comparator: Ezetimibe (Q2W) - Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Active Comparator: Ezetimibe (QM) - Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Experimental: Evolocumab Q2W - Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

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


Other interventions: Evolocumab
Subcutaneous injection

Treatment: Drugs: Placebo to Evolocumab
Subcutaneous injection

Treatment: Drugs: Ezetimibe
Tablet for oral administration

Treatment: Drugs: Placebo to Ezetimibe
Tablet for oral administration
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in LDL-C at Week 12
Timepoint [1] 0 0
Baseline and Week 12
Primary outcome [2] 0 0
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Timepoint [2] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [1] 0 0
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Timepoint [1] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [2] 0 0
Change From Baseline in LDL-C at Week 12
Timepoint [2] 0 0
Baseline and Week 12
Secondary outcome [3] 0 0
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
Timepoint [3] 0 0
Weeks 10 and 12
Secondary outcome [4] 0 0
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Timepoint [5] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [6] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Timepoint [7] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [8] 0 0
Percent Change From Baseline in Apolipoprotein B at Week 12
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12
Timepoint [9] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [10] 0 0
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12
Timepoint [10] 0 0
Baseline and Week 12
Secondary outcome [11] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Timepoint [11] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [12] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Timepoint [12] 0 0
Baseline and Week 12
Secondary outcome [13] 0 0
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Timepoint [13] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [14] 0 0
Percent Change From Baseline in Lipoprotein (a) at Week 12
Timepoint [14] 0 0
Baseline and Week 12
Secondary outcome [15] 0 0
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Timepoint [15] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [16] 0 0
Percent Change From Baseline in Triglycerides at Week 12
Timepoint [16] 0 0
Baseline and Week 12
Secondary outcome [17] 0 0
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Timepoint [17] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [18] 0 0
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Timepoint [18] 0 0
Baseline and Week 12
Secondary outcome [19] 0 0
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12
Timepoint [19] 0 0
Baseline and Weeks 10 and 12
Secondary outcome [20] 0 0
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12
Timepoint [20] 0 0
Baseline and Week 12

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/11/2013
Sample size
Target
Accrual to date
Final
307
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Milton
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment hospital [4] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
2015 - Camperdown
Recruitment postcode(s) [2] 0 0
4064 - Milton
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maine
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Belgium
State/province [12] 0 0
Brussels
Country [13] 0 0
Belgium
State/province [13] 0 0
Gent
Country [14] 0 0
Belgium
State/province [14] 0 0
La Louvière
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Denmark
State/province [17] 0 0
Aalborg
Country [18] 0 0
Denmark
State/province [18] 0 0
Ballerup
Country [19] 0 0
Denmark
State/province [19] 0 0
Vejle
Country [20] 0 0
France
State/province [20] 0 0
Lille Cedex
Country [21] 0 0
France
State/province [21] 0 0
Paris Cedex 13
Country [22] 0 0
France
State/province [22] 0 0
Vénissieux
Country [23] 0 0
Germany
State/province [23] 0 0
Bad Krozingen
Country [24] 0 0
Germany
State/province [24] 0 0
Dresden
Country [25] 0 0
Germany
State/province [25] 0 0
Heppenheim
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
Hong Kong
State/province [27] 0 0
New Territories
Country [28] 0 0
Netherlands
State/province [28] 0 0
Alkmaar
Country [29] 0 0
Netherlands
State/province [29] 0 0
Amsterdam
Country [30] 0 0
Netherlands
State/province [30] 0 0
Groningen
Country [31] 0 0
Poland
State/province [31] 0 0
Lodz
Country [32] 0 0
Poland
State/province [32] 0 0
Warszawa
Country [33] 0 0
South Africa
State/province [33] 0 0
Gauteng
Country [34] 0 0
South Africa
State/province [34] 0 0
Western Cape
Country [35] 0 0
Spain
State/province [35] 0 0
Andalucía
Country [36] 0 0
Spain
State/province [36] 0 0
Aragón
Country [37] 0 0
Spain
State/province [37] 0 0
Cataluña
Country [38] 0 0
Switzerland
State/province [38] 0 0
Lugano
Country [39] 0 0
Switzerland
State/province [39] 0 0
Reinach
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Liverpool
Country [41] 0 0
United Kingdom
State/province [41] 0 0
London
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Telford
Country [43] 0 0
United Kingdom
State/province [43] 0 0
West Bromwich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01763905
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01763905