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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03175367




Registration number
NCT03175367
Ethics application status
Date submitted
1/06/2017
Date registered
1/06/2017
Date last updated
13/09/2018

Titles & IDs
Public title
Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Doses and Dose Regimens of Evinacumab in Patients With Persistent Hypercholesterolemia Despite Maximally Tolerated Lipid Modifying Therapy
Secondary ID [1] 0 0
2017-001508-31
Secondary ID [2] 0 0
R1500-CL-1643
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 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 - Evinacumab
Treatment: Drugs - Matching placebo
Other interventions - Background Lipid Modifying Therapy (LMT)

Experimental: Group A: dosing regimen 1 - SC Evinacumab once QW for 16 weeks

Experimental: Group A: dosing regimen 2 - SC Evinacumab once Q2W for 16 weeks (alternating with matching placebo on opposite weeks)

Experimental: Group A: dosing regimen 3 - SC Evinacumab once QW for 16 weeks

Experimental: Group A: matching placebo - Placebo SC once QW for 16 weeks

Experimental: Group B: dosing regimen 1 - Intravenous (IV) Evinacumab once Q4W for 24 weeks

Experimental: Group B: dosing regimen 2 - IV Evinacumab once Q4W for 24 weeks

Experimental: Group B: matching placebo - Placebo IV once Q4W for 24 weeks


Treatment: Drugs: Evinacumab
SC or IV administration

Treatment: Drugs: Matching placebo
SC or IV administration

Other interventions: Background Lipid Modifying Therapy (LMT)
All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.

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 in calculated low-density lipoprotein cholesterol (LDL-C) from baseline to week 16 in the intent-to-treat (ITT) population, using all LDL-C values regardless of adherence to treatment and subsequent therapies
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [1] 0 0
Percent change in Apolipoprotein B (ApoB) from baseline to week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [2] 0 0
Percent change in non high-density lipoprotein cholesterol (HDL-C) from baseline to week 16
Timepoint [2] 0 0
Baseline to Week 16
Secondary outcome [3] 0 0
Percent change in total cholesterol (TC) from baseline to week 16
Timepoint [3] 0 0
Baseline to Week 16
Secondary outcome [4] 0 0
Proportion of patients with = 30% reduction in calculated LDL-C at week 16
Timepoint [4] 0 0
Baseline to Week 16
Secondary outcome [5] 0 0
Proportion of patients with = 50% reduction in calculated LDL-C at week 16
Timepoint [5] 0 0
Baseline to Week 16
Secondary outcome [6] 0 0
Percent change in triglycerides (TGs) from baseline to week 16
Timepoint [6] 0 0
Baseline to Week 16
Secondary outcome [7] 0 0
Percent change in Lipoprotein(a) [(Lp(a)] from baseline to week 16
Timepoint [7] 0 0
Baseline to Week 16
Secondary outcome [8] 0 0
Proportion of patients with calculated LDL-C < 100 mg/dL (2.59 mmol/L) at week 16
Timepoint [8] 0 0
Baseline and at Week 16
Secondary outcome [9] 0 0
Proportion of patients with calculated LDL-C < 70 mg/dL (1.181 mmol/L) at week 16
Timepoint [9] 0 0
Baseline and at Week 16
Secondary outcome [10] 0 0
Percent change in calculated LDL-C from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [10] 0 0
Baseline to Week 24
Secondary outcome [11] 0 0
Percent change in calculated ApoB from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [11] 0 0
Baseline to Week 24
Secondary outcome [12] 0 0
Percent change in calculated non-HDL-C from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [12] 0 0
Baseline to Week 24
Secondary outcome [13] 0 0
Percent change in calculated TC from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [13] 0 0
Baseline to Week 24
Secondary outcome [14] 0 0
Percent change in calculated TG from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [14] 0 0
Baseline to Week 24
Secondary outcome [15] 0 0
Percent change in calculated Lp(a) from baseline to week 24 - (only applicable to those participants receiving IV route of study treatment administration)
Timepoint [15] 0 0
Baseline to Week 24

Eligibility
Key inclusion criteria
The inclusion/ exclusion criteria below, include, but are not limited to, the following:

Key

1. Men and women, ages 18 through 75 at the screening visit

2. Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD

3. A history of clinical ASCVD, for those patients who are non-HeFH.

4. Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at
screening

5. Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for
at least 8 weeks prior to the screening visit

6. Serum LDL-C = 100 mg/dL at screening (1 repeat lab is allowed)

7. Provide signed informed consent

Key
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known history of homozygous FH (clinically, or by previous genotyping)

2. Presence of any clinically significant uncontrolled endocrine disease known to
influence serum lipids or lipoproteins

3. Newly diagnosed diabetes (within 3 months prior to screening)

4. Use of thyroid medications (except for replacement therapy which has been stable for
at least 12 weeks before screening)

5. Laboratory findings during screening period (not including randomization labs):

1. Triglycerides > 400 mg/dL (> 4.52 mmol/L) for patients without a known history of
diabetes mellitus; OR Triglycerides > 300 mg/dL (> 3.39 mmol/L) for patients with
a known history of diabetes mellitus

2. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
(associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)

3. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women
of childbearing potential

4. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2

5. TSH > 1.5 x ULN

6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN

6. Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening
visit or time of randomization

7. History of heart failure (New York Heart Association [NYHA] Class II-IV) within 12
months before screening

8. History of MI, unstable angina leading to hospitalization, CABG surgery, PCI,
uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, TIA, carotid
revascularization, endovascular procedure or surgical intervention for peripheral
vascular disease within 3 months prior screening

9. History of cancer within the past 5 years (except for adequately treated basal cell
skin cancer, squamous cell skin cancer, or in situ cervical cancer)

10. Having received LDL apheresis within 2 months before screening

11. Pregnant or breast-feeding women

12. Women of childbearing potential who are unwilling to practice a highly effective birth
control method

13. Sexually active men unwilling to use acceptable birth control.

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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Redcliffe Hospital - Redcliffe
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
1020 - Redcliffe
Recruitment postcode(s) [3] 0 0
4020 - Redcliffe
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
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
Texas
Country [11] 0 0
Austria
State/province [11] 0 0
Tyrol
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague 3
Country [15] 0 0
Czechia
State/province [15] 0 0
Prague
Country [16] 0 0
Denmark
State/province [16] 0 0
Esbjerg
Country [17] 0 0
Denmark
State/province [17] 0 0
Herning
Country [18] 0 0
Israel
State/province [18] 0 0
H_olon
Country [19] 0 0
Israel
State/province [19] 0 0
Nahariya
Country [20] 0 0
Italy
State/province [20] 0 0
Pisa
Country [21] 0 0
Italy
State/province [21] 0 0
Rimini
Country [22] 0 0
Italy
State/province [22] 0 0
Rome
Country [23] 0 0
Netherlands
State/province [23] 0 0
Hoorn Noord-Hollan
Country [24] 0 0
Netherlands
State/province [24] 0 0
Zeeland
Country [25] 0 0
Netherlands
State/province [25] 0 0
Amsterdam
Country [26] 0 0
New Zealand
State/province [26] 0 0
Canterbury
Country [27] 0 0
New Zealand
State/province [27] 0 0
Papamoa
Country [28] 0 0
New Zealand
State/province [28] 0 0
Tauranga
Country [29] 0 0
Norway
State/province [29] 0 0
Hamar
Country [30] 0 0
Norway
State/province [30] 0 0
Oslo
Country [31] 0 0
Poland
State/province [31] 0 0
Dolnoslaskie
Country [32] 0 0
Poland
State/province [32] 0 0
Podlaskie
Country [33] 0 0
Poland
State/province [33] 0 0
Ruda Slaska
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Kemerovo
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Novosibirsk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Rostov-on-Don
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Saint Petersburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Samara
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Tomsk
Country [41] 0 0
South Africa
State/province [41] 0 0
Gauteng
Country [42] 0 0
South Africa
State/province [42] 0 0
West Gauteng
Country [43] 0 0
South Africa
State/province [43] 0 0
Western Cape
Country [44] 0 0
South Africa
State/province [44] 0 0
Cape Town
Country [45] 0 0
South Africa
State/province [45] 0 0
Parow
Country [46] 0 0
Spain
State/province [46] 0 0
A Coruna
Country [47] 0 0
Spain
State/province [47] 0 0
Aragon
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Córdoba
Country [50] 0 0
Spain
State/province [50] 0 0
Granada
Country [51] 0 0
Sweden
State/province [51] 0 0
Stockholm

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to evaluate the reduction of low-density lipoprotein
cholesterol (LDL-C) by evinacumab in comparison to placebo after 16 weeks in patients with
primary hypercholesterolemia (heterozygous familial hypercholesterolemia [HeFH], or non-HeFH
with a history of clinical atherosclerotic cardiovascular disease [clinical ASCVD]) with
LDL-C = 100 mg/dL (2.59 mmol/L) despite maximally tolerated statin and proprotein convertase
subtilisin/kexin type 9 (PCSK9) inhibitor therapy.
Trial website
https://clinicaltrials.gov/show/NCT03175367
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
clinicaltrials@regeneron.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable