Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

NCT03175367 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: R1500-CL-16432017-001508-31
• Study Type: interventional
• Target: 272
• Locations: 19 countries
• Sites: 93

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• 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

Study Arms (7)

Group A: dosing regimen 1

EXPERIMENTAL

SC Evinacumab QW for 16 weeks

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

Group A: dosing regimen 2

EXPERIMENTAL

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

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

Group A: dosing regimen 3

EXPERIMENTAL

SC Evinacumab QW for 16 weeks

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

Group A: matching placebo

EXPERIMENTAL

Placebo SC QW for 16 weeks

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

Group B: dosing regimen 1

EXPERIMENTAL

Intravenous (IV) Evinacumab Q4W for 24 weeks

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

Group B: dosing regimen 2

EXPERIMENTAL

IV Evinacumab Q4W for 24 weeks

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

Group B: matching placebo

EXPERIMENTAL

Placebo IV Q4W for 24 weeks

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

Interventions

Evinacumab DRUG

SC or IV administration

Also known as: REGN1500

Group A: dosing regimen 1; Group A: dosing regimen 2; Group A: dosing regimen 3; Group B: dosing regimen 1; Group B: dosing regimen 2

Matching placebo DRUG

SC or IV administration

Group A: matching placebo; Group B: matching placebo

Background Lipid Modifying Therapy (LMT) 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 1; Group A: dosing regimen 2; Group A: dosing regimen 3; Group A: matching placebo; Group B: dosing regimen 1; Group B: dosing regimen 2; Group B: matching placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Men and women, ages 18 through 80 at the screening visit
• Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD
• A history of clinical ASCVD, for those patients who are non-HeFH.
• Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at screening
• For those patients with HeFH who are not receiving a statin at screening, documentation of inability to tolerate at least 2 statins.
• 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
• For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at screening (1 repeat lab is allowed)
• For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)
• Provide signed informed consent
• Known history of homozygous FH (clinically, or by previous genotyping)
• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
• Newly diagnosed diabetes (within 3 months prior to screening)
• Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before screening)
• Laboratory findings during screening period (not including randomization labs):
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (95)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Office of Dr. John D Homan MD

Newport Beach, California, 92663-3668, United States

Location

Preventive Cardiology Inc

Boca Raton, Florida, 33434, United States

Location

Care Research Center Inc

Doral, Florida, 33166, United States

Location

Florida Lipid Institute

Winter Park, Florida, 32792, United States

Location

St. Vincent Medical Group, Inc

Indianapolis, Indiana, 46290, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

EMMC Northeast Cardiology Assocites

Bangor, Maine, 04401, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Heart Health Cardiology

Grand Rapids, Michigan, 49546, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mt Sinai Ichan Medical Institute

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Rowan Diagnostic Clinic

Salisbury, North Carolina, 28144, United States

Location

Capital Area Research, LLC

Camp Hill, Pennsylvania, 17011, United States

Location

The University Of Texas Health Science Center Houston

Houston, Texas, 77030, United States

Location

San Antonio Premiere Internal Medicine

San Antonio, Texas, 78220, United States

Location

Clear Clinical Research, LLC

Schertz, Texas, 78154, United States

Location

PharmaTex Research

Tyler, Texas, 75701, United States

Location

Wasatch Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Redcliffe Hospital

Redcliffe, Queensland, 1020, Australia

Location

University Hospital Innsbruck - Tyrolean Hospital

Innsbruck, Tyrol, 6020, Austria

Location

Medizinische Universitaetsklinik Graz

Graz, A-8036, Austria

Location

Robarts Research Institute

London, Ontario, N6A 5B7, Canada

Location

SKDS Research Inc.

Newmarket, Ontario, L3Y 5G8, Canada

Location

Centre Etudes Cliniques Econogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Clinique des maladies lipidiques de Quebec

Québec, Quebec, G1V 4W2, Canada

Location

CCR Prague, S.R.O

Prague, Prague 3, 13000, Czechia

Location

Univerzita Karlova v Praze 1 Lekarska Fakulta

Karlov, Praha 2, 121 08, Czechia

Location

University Hospital, Charles University

Hradec Králové, 50008, Czechia

Location

Ikem Institut Klinicke A Experimentalni Mediciny

Prague, 14021, Czechia

Location

Sydvestjysk Sygehus

Esbjerg, 6700, Denmark

Location

Regionshospitalet Herning

Herning, 7400, Denmark

Location

Hopital G Et R Laennec

Nantes, Cedex, 44000, France

Location

Houpital Du Bocage

Dijon, 21079, France

Location

Edith Wolfson Medical Center

Holon, 58100, Israel

Location

Galilee Medical Center

Nahariya, Israel

Location

Sheba Mc

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center, Cardiovascular Research Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliero Universitaria Federico II di Napoli

Napoli, 80131, Italy

Location

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

Pisa, 56126, Italy

Location

Ausl Della Romagna-Ospedale Degli Infermi

Rimini, 47923, Italy

Location

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

Rome, 00185, Italy

Location

Tokyo-Eki Center-building Clinic

Chūōku, 103-0027, Japan

Location

Shonan Fujisawa Tokushukai Hospital

Fujisawa-shi, 251-0041, Japan

Location

Minamino Cardiovascular Hospital

Hachiōji, 192-0918, Japan

Location

Saitama Medical University Hospital

Iruma-gun, 350-0495, Japan

Location

Istishari Hospital

Amman, 11184, Jordan

Location

King Abdullah University Hospital-1

Irbid, 22110, Jordan

Location

King Abdullah University Hospital-2

Irbid, 22110, Jordan

Location

King Abdullah University Hospital

Irbid, 22110, Jordan

Location

VOC Hoorn

Hoorn, Hoorn Noord-Hollan, 1624 NP, Netherlands

Location

Admiraal de Ruyter Ziekenhuis

Goes, Zeeland, 4462 RA, Netherlands

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Utrech - Locatie AZU

Utrecht, Netherlands

Location

Lipid and Diabetes Research Group

Christchurch, Canterbury, 8011, New Zealand

Location

Papamoa Pines Medical Centre

Papamoa, 3118, New Zealand

Location

Clinical Horizons NZ Ltd

Tauranga, 3112, New Zealand

Location

M3 Helse AS

Oslo, 0373, Norway

Location

Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED

Żarów, Lower Silesian Voivodeship, 58-130, Poland

Location

Nzoz Przychodnia Specjalistyczna

Ruda Slaska, Podlaskie Voivodeship, 41709, Poland

Location

Wojewodzki Szpital Specjalistyczny

Bytom, Poland

Location

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

Zabrze, 41-800, Poland

Location

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

Kemerovo, 65000, Russia

Location

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

Moscow, 119990, Russia

Location

Federal State Budget Institution Out-patient Clinic 3

Moscow, 129090, Russia

Location

NII of Therapy and Preventive Medicine

Novosibirsk, 630089, Russia

Location

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

Rostov-on-Don, 34406, Russia

Location

Limmited Liability Company International Medical Centre SOGAZ

Saint Petersburg, 191186, Russia

Location

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

Saint Petersburg, 194291, Russia

Location

LLC- Institute of Medical Research

Saint Petersburg, 196084, Russia

Location

Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic

Saint Petersburg, 197110, Russia

Location

Samara Regional Clinical Cardiologic Dispensary

Samara, 443070, Russia

Location

Cardiology Research Institute

Tomsk, 34012, Russia

Location

The Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, 2000, South Africa

Location

Jongaie Research

Pretoria, West Gauteng, 182, South Africa

Location

Dr JM Engelbrecht Trial Site

Cape Town, Western Cape, 713, South Africa

Location

University of Cape Town

Cape Town, 7925, South Africa

Location

TREAD Research CC

Parow, 7500, South Africa

Location

Hospital Universitario A Coruna

A Coruña, A Coruna, 15001, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves (HUVN)

Granada, 18014, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Karolinska University Hospital

Malmo, Sweden

Location

Akardo MedSite

Stockholm, 11446, Sweden

Location

Karolinska Institutet

Stockholm, SE-182 88, Sweden

Location

Akademiska sjukhuset

Uppsala, 75185, Sweden

Location

Royal Free Hospital-Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

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

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37703006 DERIVED

• 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.

  PMID: 33196153 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evinacumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

8447346643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: November 10, 2017
• Primary Completion: May 22, 2020
• Study Completion: December 14, 2020
• Last Updated: February 10, 2023
• Results First Posted: February 10, 2023

Record last verified: 2023-01

Locations

IL (4); NO (1); SE (4); CZ (4); JO (4); NZ (3); IT (4); AU (2); US (23); DK (2); RU (11); GB (2); PL (4); CA (4); FR (2); JP (4); NL (4); ZA (5); ES (6)