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Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

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ClinicalTrials.gov Identifier: NCT03175367
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Drug: Evinacumab Drug: Matching placebo Other: Background Lipid Modifying Therapy (LMT) Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 2, 2018
Estimated Primary Completion Date : October 21, 2019
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A: dosing regimen 1
SC Evinacumab once QW for 16 weeks
Drug: Evinacumab
SC or IV administration
Other Name: REGN1500

Other: 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.

Experimental: Group A: dosing regimen 2
SC Evinacumab once Q2W for 16 weeks (alternating with matching placebo on opposite weeks)
Drug: Evinacumab
SC or IV administration
Other Name: REGN1500

Drug: Matching placebo
SC or IV administration

Other: 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.

Experimental: Group A: dosing regimen 3
SC Evinacumab once QW for 16 weeks
Drug: Evinacumab
SC or IV administration
Other Name: REGN1500

Other: 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.

Experimental: Group A: matching placebo
Placebo SC once QW for 16 weeks
Drug: Matching placebo
SC or IV administration

Other: 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.

Experimental: Group B: dosing regimen 1
Intravenous (IV) Evinacumab once Q4W for 24 weeks
Drug: Evinacumab
SC or IV administration
Other Name: REGN1500

Other: 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.

Experimental: Group B: dosing regimen 2
IV Evinacumab once Q4W for 24 weeks
Drug: Evinacumab
SC or IV administration
Other Name: REGN1500

Other: 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.

Experimental: Group B: matching placebo
Placebo IV once Q4W for 24 weeks
Drug: Matching placebo
SC or IV administration

Other: 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.




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline to Week 16 ]

Secondary Outcome Measures :
  1. Percent change in Apolipoprotein B (ApoB) from baseline to week 16 [ Time Frame: Baseline to Week 16 ]
  2. Percent change in non high-density lipoprotein cholesterol (HDL-C) from baseline to week 16 [ Time Frame: Baseline to Week 16 ]
  3. Percent change in total cholesterol (TC) from baseline to week 16 [ Time Frame: Baseline to Week 16 ]
  4. Proportion of patients with ≥ 30% reduction in calculated LDL-C at week 16 [ Time Frame: Baseline to Week 16 ]
  5. Proportion of patients with ≥ 50% reduction in calculated LDL-C at week 16 [ Time Frame: Baseline to Week 16 ]
  6. Percent change in triglycerides (TGs) from baseline to week 16 [ Time Frame: Baseline to Week 16 ]
  7. Percent change in Lipoprotein(a) [(Lp(a)] from baseline to week 16 [ Time Frame: Baseline to Week 16 ]
  8. Proportion of patients with calculated LDL-C < 100 mg/dL (2.59 mmol/L) at week 16 [ Time Frame: Baseline and at Week 16 ]
  9. Proportion of patients with calculated LDL-C < 70 mg/dL (1.181 mmol/L) at week 16 [ Time Frame: Baseline and at Week 16 ]
  10. Percent change in calculated LDL-C from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)

  11. Percent change in calculated ApoB from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)

  12. Percent change in calculated non-HDL-C from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)

  13. Percent change in calculated TC from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)

  14. Percent change in calculated TG from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)

  15. Percent change in calculated Lp(a) from baseline to week 24 [ Time Frame: Baseline to Week 24 ]
    (only applicable to those participants receiving IV route of study treatment administration)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Key Inclusion Criteria:

  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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03175367


Contacts
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

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Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03175367     History of Changes
Other Study ID Numbers: R1500-CL-1643
2017-001508-31 ( EudraCT Number )
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases