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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01984424




Registration number
NCT01984424
Ethics application status
Date submitted
8/11/2013
Date registered
14/11/2013
Date last updated
29/11/2018

Titles & IDs
Public title
Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3
Scientific title
A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects
Secondary ID [1] 0 0
2013-000935-29
Secondary ID [2] 0 0
20120332
Universal Trial Number (UTN)
Trial acronym
GAUSS-3
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
Treatment: Drugs - Atorvastatin
Treatment: Drugs - Placebo to Atorvastatin
Other interventions - Placebo to Ezetimibe
Treatment: Drugs - Ezetimibe
Other interventions - Placebo to Evolocumab
Treatment: Drugs - Evolocumab

Other: Part A: Atorvastatin 20 mg => Placebo - Participants received atorvastatin 20 mg orally for 10 weeks (period 1) followed by placebo orally for 10 weeks (period 2), separated by a 2-week washout period.

Other: Part A: Placebo => Atorvastatin 20 mg - Participants received placebo orally for 10 weeks (period 1) followed by atorvastatin 20 mg orally for 10 weeks (period 2), separated by a 2-week washout period.

Active comparator: Part B: Ezetimibe - Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.

Experimental: Part B: Evolocumab - Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.

Experimental: Part C: Open-label Evolocumab - Participants who completed part B and were eligible to proceed to open-label extension part C and could choose quarterly between evolocumab 420 mg once a month or evolocumab 140 mg every 2 weeks for up to 2 years.


Treatment: Drugs: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets

Treatment: Drugs: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets

Other interventions: Placebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.

Treatment: Drugs: Ezetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.

Other interventions: Placebo to Evolocumab
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)

Treatment: Drugs: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Timepoint [1] 0 0
Baseline and weeks 22 and 24
Primary outcome [2] 0 0
Percent Change From Baseline in LDL-C at Week 24
Timepoint [2] 0 0
Baseline and week 24
Secondary outcome [1] 0 0
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Timepoint [1] 0 0
Baselie and weeks 22 and 24
Secondary outcome [2] 0 0
Change From Baseline in LDL-C at Week 24
Timepoint [2] 0 0
Baseline and week 24
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL
Timepoint [3] 0 0
Weeks 22 and 24
Secondary outcome [4] 0 0
Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24
Timepoint [5] 0 0
Baseline and weeks 22 and 24
Secondary outcome [6] 0 0
Percent Change From Baseline in Total Cholesterol at Week 24
Timepoint [6] 0 0
Baseline and week 24
Secondary outcome [7] 0 0
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24
Timepoint [7] 0 0
Baseline and weeks 22 and 24
Secondary outcome [8] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24
Timepoint [8] 0 0
Baseline and week 24
Secondary outcome [9] 0 0
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24
Timepoint [9] 0 0
Baseline and weeks 22 and 24
Secondary outcome [10] 0 0
Percent Change From Baseline in Apolipoprotein B at Week 24
Timepoint [10] 0 0
Baseline and week 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24
Timepoint [11] 0 0
Baseline and weeks 22 and 24
Secondary outcome [12] 0 0
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24
Timepoint [12] 0 0
Baseline and week 24
Secondary outcome [13] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24
Timepoint [13] 0 0
Baseline and Weeks 22 and 24
Secondary outcome [14] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24
Timepoint [14] 0 0
Baseline and week 24
Secondary outcome [15] 0 0
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24
Timepoint [15] 0 0
Baseline and Weeks 22 and 24
Secondary outcome [16] 0 0
Percent Change From Baseline in Lipoprotein(a) at Week 24
Timepoint [16] 0 0
Baseline and week 24
Secondary outcome [17] 0 0
Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24
Timepoint [17] 0 0
Baseline and weeks 22 and 24
Secondary outcome [18] 0 0
Percent Change From Baseline in Triglycerides at Week 24
Timepoint [18] 0 0
Baseline and week 24
Secondary outcome [19] 0 0
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24
Timepoint [19] 0 0
Baseline and weeks 22 and 24
Secondary outcome [20] 0 0
Percent Change From Baseline in HDL-C at Week 24
Timepoint [20] 0 0
Baseline and week 24
Secondary outcome [21] 0 0
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24
Timepoint [21] 0 0
Baseline and weeks 22 and 24
Secondary outcome [22] 0 0
Percent Change From Baseline in VLDL-C at Week 24
Timepoint [22] 0 0
Baseline and week 24

Eligibility
Key inclusion criteria
* Male or female = 18 to = 80 years of age
* Subject not at LDL-C goal
* History of statin intolerance
* 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
10/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/11/2017
Sample size
Target
Accrual to date
Final
511
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Woolloongabba
Recruitment hospital [3] 0 0
Research Site - Ashford
Recruitment postcode(s) [1] 0 0
2015 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5035 - Ashford
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
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Czechia
State/province [18] 0 0
Hradec Kralove
Country [19] 0 0
Czechia
State/province [19] 0 0
Praha 2
Country [20] 0 0
Czechia
State/province [20] 0 0
Praha 4
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus N
Country [22] 0 0
Denmark
State/province [22] 0 0
Glostrup
Country [23] 0 0
France
State/province [23] 0 0
Nantes Cedex 1
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 13
Country [25] 0 0
France
State/province [25] 0 0
Vénissieux
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Köln
Country [28] 0 0
Germany
State/province [28] 0 0
München
Country [29] 0 0
Italy
State/province [29] 0 0
Bologna
Country [30] 0 0
Italy
State/province [30] 0 0
Cagliari
Country [31] 0 0
Italy
State/province [31] 0 0
Cinisello Balsamo (MI)
Country [32] 0 0
Italy
State/province [32] 0 0
Ferrara
Country [33] 0 0
Italy
State/province [33] 0 0
Perugia
Country [34] 0 0
Italy
State/province [34] 0 0
Pisa
Country [35] 0 0
Netherlands
State/province [35] 0 0
Amsterdam
Country [36] 0 0
Netherlands
State/province [36] 0 0
Rotterdam
Country [37] 0 0
Netherlands
State/province [37] 0 0
Zwijndrecht
Country [38] 0 0
New Zealand
State/province [38] 0 0
Christchurch
Country [39] 0 0
Norway
State/province [39] 0 0
Oslo
Country [40] 0 0
Norway
State/province [40] 0 0
Ålesund
Country [41] 0 0
South Africa
State/province [41] 0 0
Gauteng
Country [42] 0 0
South Africa
State/province [42] 0 0
Western Cape
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Birmingham
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Glasgow
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Newcastle upon Tyne

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study was to evaluate the effect of 24 weeks of evolocumab administered subcutaneously (SC) every month, compared with ezetimibe, on low-density lipoprotein cholesterol (LDL-C) levels in adults with high cholesterol who are unable to tolerate an effective dose of a statin due to muscle-related side effects (MRSE).
Trial website
https://clinicaltrials.gov/study/NCT01984424
Trial related presentations / publications
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.
Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceska R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA; GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016 Apr 19;315(15):1580-90. doi: 10.1001/jama.2016.3608.
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/study/NCT01984424