Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

NCT ID: NCT03175367

Last Updated: 2023-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-10
• Study Completion Date: 2020-12-14

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A: dosing regimen 1

SC Evinacumab QW for 16 weeks

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group A: dosing regimen 2

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

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group A: dosing regimen 3

SC Evinacumab QW for 16 weeks

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group A: matching placebo

Placebo SC QW for 16 weeks

Group Type: EXPERIMENTAL

Matching placebo

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group B: dosing regimen 1

Intravenous (IV) Evinacumab Q4W for 24 weeks

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group B: dosing regimen 2

IV Evinacumab Q4W for 24 weeks

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Group B: matching placebo

Placebo IV Q4W for 24 weeks

Group Type: EXPERIMENTAL

Matching placebo

Intervention Type: DRUG

SC or IV administration

Background Lipid Modifying Therapy (LMT)

Intervention Type: OTHER

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.

Interventions

Evinacumab

SC or IV administration

Intervention Type: DRUG

Matching placebo

SC or IV administration

Intervention Type: DRUG

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 Type: OTHER

Other Intervention Names

REGN1500

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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

Heart Health Cardiology

Grand Rapids, Michigan, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mt Sinai Ichan Medical Institute

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Rowan Diagnostic Clinic

Salisbury, North Carolina, United States

Capital Area Research, LLC

Camp Hill, Pennsylvania, United States

The University Of Texas Health Science Center Houston

Houston, Texas, United States

San Antonio Premiere Internal Medicine

San Antonio, Texas, United States

Clear Clinical Research, LLC

Schertz, Texas, United States

PharmaTex Research

Tyler, Texas, United States

Wasatch Clinical Research

Salt Lake City, Utah, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Redcliffe Hospital

Redcliffe, Queensland, Australia

University Hospital Innsbruck - Tyrolean Hospital

Innsbruck, Tyrol, Austria

Medizinische Universitaetsklinik Graz

Graz, , Austria

Robarts Research Institute

London, Ontario, Canada

SKDS Research Inc.

Newmarket, Ontario, Canada

Centre Etudes Cliniques Econogene-21

Chicoutimi, Quebec, Canada

Clinique des maladies lipidiques de Quebec

Québec, Quebec, Canada

CCR Prague, S.R.O

Prague, Prague 3, Czechia

Univerzita Karlova v Praze 1 Lekarska Fakulta

Karlov, Praha 2, Czechia

University Hospital, Charles University

Hradec Králové, , Czechia

Ikem Institut Klinicke A Experimentalni Mediciny

Prague, , Czechia

Sydvestjysk Sygehus

Esbjerg, , Denmark

Regionshospitalet Herning

Herning, , Denmark

Hopital G Et R Laennec

Nantes, Cedex, France

Houpital Du Bocage

Dijon, , France

Edith Wolfson Medical Center

Holon, , Israel

Galilee Medical Center

Nahariya, , Israel

Sheba Mc

Ramat Gan, , Israel

Sourasky Medical Center, Cardiovascular Research Center

Tel Aviv, , Israel

Azienda Ospedaliero Universitaria Federico II di Napoli

Napoli, , Italy

Fondazione Toscana Gabriele Monasterio Per La Ricerca Medica E Di Sanita Pubblica

Pisa, , Italy

Ausl Della Romagna-Ospedale Degli Infermi

Rimini, , Italy

Dipartimento di Medicina Traslazionale e di Precisione dell'Università degli Studi di

Rome, , Italy

Tokyo-Eki Center-building Clinic

Chūōku, , Japan

Shonan Fujisawa Tokushukai Hospital

Fujisawa-shi, , Japan

Minamino Cardiovascular Hospital

Hachiōji, , Japan

Saitama Medical University Hospital

Iruma-gun, , Japan

Istishari Hospital

Amman, , Jordan

King Abdullah University Hospital-1

Irbid, , Jordan

King Abdullah University Hospital-2

Irbid, , Jordan

King Abdullah University Hospital

Irbid, , Jordan

VOC Hoorn

Hoorn, Hoorn Noord-Hollan, Netherlands

Admiraal de Ruyter Ziekenhuis

Goes, Zeeland, Netherlands

Academic Medical Center

Amsterdam, , Netherlands

Universitair Medisch Centrum Utrech - Locatie AZU

Utrecht, , Netherlands

Lipid and Diabetes Research Group

Christchurch, Canterbury, New Zealand

Papamoa Pines Medical Centre

Papamoa, , New Zealand

Clinical Horizons NZ Ltd

Tauranga, , New Zealand

M3 Helse AS

Oslo, , Norway

Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED

Żarów, Lower Silesian Voivodeship, Poland

Nzoz Przychodnia Specjalistyczna

Ruda Slaska, Podlaskie Voivodeship, Poland

Wojewodzki Szpital Specjalistyczny

Bytom, , Poland

Slaskie Centrum Chorob Serca, III Katedra i Oddzial Kliniczny Kardiologii SUM- Oddzial Chorob Serca i Naczyn

Zabrze, , Poland

Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovacsular Disease

Kemerovo, , Russia

National Research Center For Preventative Medicine of Federal Agency of High Technology Medical Aid

Moscow, , Russia

Federal State Budget Institution Out-patient Clinic 3

Moscow, , Russia

NII of Therapy and Preventive Medicine

Novosibirsk, , Russia

Municipal Medical and Prophylactic Institution - City Hospital for Emergency Care No.2

Rostov-on-Don, , Russia

Limmited Liability Company International Medical Centre SOGAZ

Saint Petersburg, , Russia

Federal State Institution of Healthcare Clinical Hospital #122 N.A.L.G Sokolov

Saint Petersburg, , Russia

LLC- Institute of Medical Research

Saint Petersburg, , Russia

Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic

Saint Petersburg, , Russia

Samara Regional Clinical Cardiologic Dispensary

Samara, , Russia

Cardiology Research Institute

Tomsk, , Russia

The Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, South Africa

Jongaie Research

Pretoria, West Gauteng, South Africa

Dr JM Engelbrecht Trial Site

Cape Town, Western Cape, South Africa

University of Cape Town

Cape Town, , South Africa

TREAD Research CC

Parow, , South Africa

Hospital Universitario A Coruna

A Coruña, A Coruna, Spain

Hospital Universitario Miguel Servet

Zaragoza, Aragon, Spain

Hospital Universitario de Bellvitge

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital Universitario Virgen de las Nieves (HUVN)

Granada, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Karolinska University Hospital

Malmo, , Sweden

Akardo MedSite

Stockholm, , Sweden

Karolinska Institutet

Stockholm, , Sweden

Akademiska sjukhuset

Uppsala, , Sweden

Royal Free Hospital-Royal Free London NHS Foundation Trust

London, , United Kingdom

Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United States; Australia; Austria; Canada; Czechia; Denmark; France; Israel; Italy; Japan; Jordan; Netherlands; New Zealand; Norway; Poland; Russia; South Africa; Spain; Sweden; United Kingdom

References

Rosenson RS, Burgess LJ, Ebenbichler CF, Baum SJ, Stroes ESG, Ali S, Khilla N, McGinniss J, Gaudet D, Pordy R. Longer-Term Efficacy and Safety of Evinacumab in Patients With Refractory Hypercholesterolemia. JAMA Cardiol. 2023 Nov 1;8(11):1070-1076. doi: 10.1001/jamacardio.2023.2921.

Reference Type: DERIVED

PMID: 37703006 (View on PubMed)

Rosenson RS, Burgess LJ, Ebenbichler CF, Baum SJ, Stroes ESG, Ali S, Khilla N, Hamlin R, Pordy R, Dong Y, Son V, Gaudet D. Evinacumab in Patients with Refractory Hypercholesterolemia. N Engl J Med. 2020 Dec 10;383(24):2307-2319. doi: 10.1056/NEJMoa2031049. Epub 2020 Nov 15.

Reference Type: DERIVED

PMID: 33196153 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001508-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R1500-CL-1643

Identifier Type: -

Identifier Source: org_study_id