Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

Treatments: Other: Background Lipid Modifying Therapy (LMT); Drug: Matching placebo; Drug: Evinacumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03175367

2017-001508-31 (EudraCT Number)

R1500-CL-1643

Details and patient eligibility

About

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.

Enrollment: 272 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Key Inclusion Criteria:

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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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272 participants in 7 patient groups

Group A: dosing regimen 1

Experimental group

Description:

SC Evinacumab QW for 16 weeks

Treatment:

Drug: Evinacumab

Other: Background Lipid Modifying Therapy (LMT)

Group A: dosing regimen 2

Experimental group

Description:

SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks)

Treatment:

Drug: Evinacumab

Other: Background Lipid Modifying Therapy (LMT)

Group A: dosing regimen 3

Experimental group

Description:

SC Evinacumab QW for 16 weeks

Treatment:

Drug: Evinacumab

Other: Background Lipid Modifying Therapy (LMT)

Group A: matching placebo

Experimental group

Description:

Placebo SC QW for 16 weeks

Treatment:

Other: Background Lipid Modifying Therapy (LMT)

Drug: Matching placebo

Group B: dosing regimen 1

Experimental group

Description:

Intravenous (IV) Evinacumab Q4W for 24 weeks

Treatment:

Drug: Evinacumab

Other: Background Lipid Modifying Therapy (LMT)

Group B: dosing regimen 2

Experimental group

Description:

IV Evinacumab Q4W for 24 weeks

Treatment:

Drug: Evinacumab

Other: Background Lipid Modifying Therapy (LMT)

Group B: matching placebo

Experimental group

Description:

Placebo IV Q4W for 24 weeks

Treatment:

Other: Background Lipid Modifying Therapy (LMT)

Drug: Matching placebo