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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/NCT03175367




Registration number
NCT03175367
Ethics application status
Date submitted
1/06/2017
Date registered
5/06/2017
Date last updated
10/02/2023

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 QW for 16 weeks

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

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

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

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

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

Experimental: Group B: matching placebo - Placebo IV 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 From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [2] 0 0
Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)
Timepoint [3] 0 0
Baseline and Week 16
Secondary outcome [4] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)
Timepoint [4] 0 0
Baseline and Week 24
Secondary outcome [5] 0 0
Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
Timepoint [5] 0 0
Week 16
Secondary outcome [6] 0 0
Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
Timepoint [6] 0 0
Week 16
Secondary outcome [7] 0 0
Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)
Timepoint [7] 0 0
Week 16
Secondary outcome [8] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)
Timepoint [8] 0 0
Baseline and Week 24
Secondary outcome [9] 0 0
Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)
Timepoint [9] 0 0
Baseline and Week 16
Secondary outcome [10] 0 0
Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)
Timepoint [10] 0 0
Baseline and Week 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)
Timepoint [11] 0 0
Baseline and Week 16
Secondary outcome [12] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)
Timepoint [12] 0 0
Baseline and Week 24
Secondary outcome [13] 0 0
Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)
Timepoint [13] 0 0
Baseline and Week 16
Secondary outcome [14] 0 0
Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)
Timepoint [14] 0 0
Baseline and 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 80 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. For those patients with HeFH who are not receiving a statin at screening,
documentation of inability to tolerate at least 2 statins.

6. 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

7. For those patients with a history of clinical ASCVD, serum LDL-C = 70 mg/dL at
screening (1 repeat lab is allowed)

8. For those patients without a history of clinical ASCVD, serum LDL-C = 100 mg/dL at
screening (1 repeat lab is allowed)

9. Provide signed informed consent

Key
Minimum age
18 Years
Maximum age
80 Years
Sex
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 III-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. Men who are sexually active with women of childbearing potential (WOCBP) and are
unwilling to consistently use condoms during the study drug treatment period
regardless of vasectomy status.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/12/2020
Sample size
Target
Accrual to date
Final
272
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 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
Maine
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
Austria
State/province [16] 0 0
Tyrol
Country [17] 0 0
Austria
State/province [17] 0 0
Graz
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Czechia
State/province [20] 0 0
Prague 3
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 2
Country [22] 0 0
Czechia
State/province [22] 0 0
Hradec Kralove
Country [23] 0 0
Czechia
State/province [23] 0 0
Prague
Country [24] 0 0
Denmark
State/province [24] 0 0
Esbjerg
Country [25] 0 0
Denmark
State/province [25] 0 0
Herning
Country [26] 0 0
France
State/province [26] 0 0
Cedex
Country [27] 0 0
France
State/province [27] 0 0
Dijon
Country [28] 0 0
Israel
State/province [28] 0 0
H_olon
Country [29] 0 0
Israel
State/province [29] 0 0
Nahariya
Country [30] 0 0
Israel
State/province [30] 0 0
Ramat Gan
Country [31] 0 0
Israel
State/province [31] 0 0
Tel Aviv
Country [32] 0 0
Italy
State/province [32] 0 0
Napoli
Country [33] 0 0
Italy
State/province [33] 0 0
Pisa
Country [34] 0 0
Italy
State/province [34] 0 0
Rimini
Country [35] 0 0
Italy
State/province [35] 0 0
Rome
Country [36] 0 0
Japan
State/province [36] 0 0
Chuo-ku
Country [37] 0 0
Japan
State/province [37] 0 0
Fujisawa-shi
Country [38] 0 0
Japan
State/province [38] 0 0
Hachioji
Country [39] 0 0
Japan
State/province [39] 0 0
Iruma-gun
Country [40] 0 0
Jordan
State/province [40] 0 0
Amman
Country [41] 0 0
Jordan
State/province [41] 0 0
Irbid
Country [42] 0 0
Netherlands
State/province [42] 0 0
Hoorn Noord-Hollan
Country [43] 0 0
Netherlands
State/province [43] 0 0
Zeeland
Country [44] 0 0
Netherlands
State/province [44] 0 0
Amsterdam
Country [45] 0 0
Netherlands
State/province [45] 0 0
Utrecht
Country [46] 0 0
New Zealand
State/province [46] 0 0
Canterbury
Country [47] 0 0
New Zealand
State/province [47] 0 0
Papamoa
Country [48] 0 0
New Zealand
State/province [48] 0 0
Tauranga
Country [49] 0 0
Norway
State/province [49] 0 0
Oslo
Country [50] 0 0
Poland
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Dolnoslaskie
Country [51] 0 0
Poland
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Podlaskie
Country [52] 0 0
Poland
State/province [52] 0 0
Bytom
Country [53] 0 0
Poland
State/province [53] 0 0
Zabrze
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Kemerovo
Country [55] 0 0
Russian Federation
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Moscow
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Novosibirsk
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Rostov-on-Don
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Saint Petersburg
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Samara
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Tomsk
Country [61] 0 0
South Africa
State/province [61] 0 0
Gauteng
Country [62] 0 0
South Africa
State/province [62] 0 0
West Gauteng
Country [63] 0 0
South Africa
State/province [63] 0 0
Western Cape
Country [64] 0 0
South Africa
State/province [64] 0 0
Cape Town
Country [65] 0 0
South Africa
State/province [65] 0 0
Parow
Country [66] 0 0
Spain
State/province [66] 0 0
A Coruna
Country [67] 0 0
Spain
State/province [67] 0 0
Aragon
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Córdoba
Country [70] 0 0
Spain
State/province [70] 0 0
Granada
Country [71] 0 0
Spain
State/province [71] 0 0
Sevilla
Country [72] 0 0
Sweden
State/province [72] 0 0
Malmö
Country [73] 0 0
Sweden
State/province [73] 0 0
Stockholm
Country [74] 0 0
Sweden
State/province [74] 0 0
Uppsala
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Newcastle Upon Tyne

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 LDL-C by evinacumab in
comparison to placebo after 16 weeks in patients with primary hypercholesterolemia (HeFH, or
non-HeFH with a history of clinical ASCVD) with persistent hypercholesterolemia despite
receiving maximally-tolerated LMT. Persistent hypercholesterolemia is defined as LDL-C =70
mg/dL (1.81 mmol/L) for those patients with clinical ASCVD and LDL-C =100 mg/dL (2.59 mmol/L)
for those patients without clinical ASCVD.
Trial website
https://clinicaltrials.gov/ct2/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
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/NCT03175367