Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Matching placebo; Drug: Evinacumab; Other: Background Lipid Modifying Therapy (LMT)

• Registration Number: NCT03175367
• Lead Sponsor: Regeneron Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-01
• Study First Submitted QC: 2017-06-01
• Study First Posted: 2017-06-05
• Study Start: 2017-11-10
• Primary Completion: 2020-05-22
• Study Completion: 2020-12-14
• Disposition First Submitted: 2021-05-20
• Results First Submitted: 2022-12-19
• Status Verified: 2023-01
• Results First Submitted QC: 2023-01-27
• Disposition First Submitted QC: 2023-01-27
• Last Update Submitted: 2023-01-27
• Results First Posted: 2023-02-10
• Disposition First Posted: 2023-02-10
• Last Update Posted: 2023-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 272

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: dosing regimen 1	Background Lipid Modifying Therapy (LMT)	SC Evinacumab QW for 16 weeks
Group A: matching placebo	Matching placebo	Placebo SC QW for 16 weeks
Group A: dosing regimen 3	Background Lipid Modifying Therapy (LMT)	SC Evinacumab QW for 16 weeks
Group B: dosing regimen 1	Background Lipid Modifying Therapy (LMT)	Intravenous (IV) Evinacumab Q4W for 24 weeks
Group A: dosing regimen 2	Background Lipid Modifying Therapy (LMT)	SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks)
Group B: matching placebo	Matching placebo	Placebo IV Q4W for 24 weeks
Group A: matching placebo	Background Lipid Modifying Therapy (LMT)	Placebo SC QW for 16 weeks
Group B: dosing regimen 2	Evinacumab	IV Evinacumab Q4W for 24 weeks
Group B: dosing regimen 2	Background Lipid Modifying Therapy (LMT)	IV Evinacumab Q4W for 24 weeks
Group B: matching placebo	Background Lipid Modifying Therapy (LMT)	Placebo IV Q4W for 24 weeks
Group A: dosing regimen 1	Evinacumab	SC Evinacumab QW for 16 weeks
Group A: dosing regimen 2	Evinacumab	SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks)
Group A: dosing regimen 3	Evinacumab	SC Evinacumab QW for 16 weeks
Group B: dosing regimen 1	Evinacumab	Intravenous (IV) Evinacumab Q4W for 24 weeks

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)	Baseline and Week 16

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)	Baseline and Week 16
Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)	Baseline and Week 24
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)	Baseline and Week 16
Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)	Baseline and Week 24
Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)	Week 16
Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)	Week 16
Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)	Week 16	Percentage of Participants with Calculated LDL-C \< 50 milligrams/deciliter (mg/dL) \[1.30 Millimoles per liter (mmol/L)\] at Week 16 (ITT Estimand)
Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)	Baseline and Week 24
Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)	Baseline and Week 16
Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)	Baseline and Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)	Baseline and Week 16
Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)	Baseline and Week 24
Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)	Baseline and Week 16
Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)	Baseline and Week 24

Trial Locations

Locations (95)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Office of Dr. John D Homan MD; 🇺🇸 Newport Beach, California, United States

Preventive Cardiology Inc; 🇺🇸 Boca Raton, Florida, United States

Care Research Center Inc; 🇺🇸 Doral, Florida, United States

Florida Lipid Institute; 🇺🇸 Winter Park, Florida, United States

St. Vincent Medical Group, Inc; 🇺🇸 Indianapolis, Indiana, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

EMMC Northeast Cardiology Assocites; 🇺🇸 Bangor, Maine, United States

University of Maryland School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

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