Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03175367
• Other study ID #: R1500-CL-1643
• Secondary ID: 2017-001508-31
• Status: Completed
• Phase: Phase 2
• Start date: November 10, 2017
• Est. completion date: December 14, 2020

Study information

• Verified date: January 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: December 14, 2020
• Est. primary completion date: May 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Evinacumab
SC or IV administration
• 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.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Redcliffe Hospital	Redcliffe	Queensland
Austria	Medizinische Universitaetsklinik Graz	Graz
Austria	University Hospital Innsbruck - Tyrolean Hospital	Innsbruck	Tyrol
Canada	Centre Etudes Cliniques Econogene-21	Chicoutimi	Quebec
Canada	Robarts Research Institute	London	Ontario
Canada	SKDS Research Inc.	Newmarket	Ontario
Canada	Clinique des maladies lipidiques de Quebec	Québec	Quebec
Czechia	University Hospital, Charles University	Hradec Kralove
Czechia	Univerzita Karlova v Praze 1 Lekarska Fakulta	Karlov	Praha 2
Czechia	Ikem Institut Klinicke A Experimentalni Mediciny	Prague
Czechia	CCR Prague, S.R.O	Praha	Prague 3
Denmark	Sydvestjysk Sygehus	Esbjerg
Denmark	Regionshospitalet Herning	Herning
France	Houpital Du Bocage	Dijon
France	Hopital G Et R Laennec	Nantes	Cedex
Israel	Edith Wolfson Medical Center	H_olon
Israel	Galilee Medical Center	Nahariya
Israel	Sheba Mc	Ramat Gan
Israel	Sourasky Medical Center, Cardiovascular Research Center	Tel Aviv
Italy	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
Japan	Tokyo-Eki Center-building Clinic	Chuo-ku
Japan	Shonan Fujisawa Tokushukai Hospital	Fujisawa-shi
Japan	Minamino Cardiovascular Hospital	Hachioji
Japan	Saitama Medical University Hospital	Iruma-gun
Jordan	Istishari Hospital	Amman
Jordan	King Abdullah University Hospital	Irbid
Jordan	King Abdullah University Hospital-1	Irbid
Jordan	King Abdullah University Hospital-2	Irbid
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Admiraal de Ruyter Ziekenhuis	Goes	Zeeland
Netherlands	VOC Hoorn	Hoorn	Hoorn Noord-Hollan
Netherlands	Universitair Medisch Centrum Utrech - Locatie AZU	Utrecht
New Zealand	Lipid and Diabetes Research Group	Christchurch	Canterbury
New Zealand	Papamoa Pines Medical Centre	Papamoa
New Zealand	Clinical Horizons NZ Ltd	Tauranga
Norway	M3 Helse AS	Oslo
Poland	Wojewodzki Szpital Specjalistyczny	Bytom
Poland	Nzoz Przychodnia Specjalistyczna	Ruda Slaska	Podlaskie
Poland	Slaskie Centrum Chorob Serca, III Katedra i Oddzial Kliniczny Kardiologii SUM- Oddzial Chorob Serca i Naczyn	Zabrze
Poland	Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED	Zarów	Dolnoslaskie
Russian Federation	Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovacsular Disease	Kemerovo
Russian Federation	Federal State Budget Institution Out-patient Clinic 3	Moscow
Russian Federation	National Research Center For Preventative Medicine of Federal Agency of High Technology Medical Aid	Moscow
Russian Federation	NII of Therapy and Preventive Medicine	Novosibirsk
Russian Federation	Municipal Medical and Prophylactic Institution - City Hospital for Emergency Care No.2	Rostov-on-Don
Russian Federation	Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic	Saint Petersburg
Russian Federation	Federal State Institution of Healthcare Clinical Hospital #122 N.A.L.G Sokolov	Saint Petersburg
Russian Federation	Limmited Liability Company International Medical Centre SOGAZ	Saint Petersburg
Russian Federation	LLC- Institute of Medical Research	Saint Petersburg
Russian Federation	Samara Regional Clinical Cardiologic Dispensary	Samara
Russian Federation	Cardiology Research Institute	Tomsk
South Africa	Dr JM Engelbrecht Trial Site	Cape Town	Western Cape
South Africa	University of Cape Town	Cape Town
South Africa	The Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
South Africa	TREAD Research CC	Parow
South Africa	Jongaie Research	Pretoria	West Gauteng
Spain	Hospital Universitario A Coruna	A Coruña	A Coruna
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	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza	Aragon
Sweden	Karolinska University Hospital	Malmö
Sweden	Akardo MedSite	Stockholm
Sweden	Karolinska Institutet	Stockholm
Sweden	Akademiska sjukhuset	Uppsala
United Kingdom	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 States	University of Maryland School of Medicine	Baltimore	Maryland
United States	EMMC Northeast Cardiology Assocites	Bangor	Maine
United States	Preventive Cardiology Inc	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	Care Research Center Inc	Doral	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	Heart Health Cardiology	Grand Rapids	Michigan
United States	The University Of Texas Health Science Center Houston	Houston	Texas
United States	St. Vincent Medical Group, Inc	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Mt Sinai Ichan Medical Institute	New York	New York
United States	Office of Dr. John D Homan MD	Newport Beach	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Rowan Diagnostic Clinic	Salisbury	North Carolina
United States	Wasatch Clinical Research	Salt Lake City	Utah
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	Florida Lipid Institute	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

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