Clinical Trials Register

Summary
EudraCT Number:	2017-001508-31
Sponsor's Protocol Code Number:	R1500-CL-1643
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-02-13
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-001508-31

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study in which patients will be assigned, by chance, to receive either the active drug Evinacumab or a dummy-drug, (a placebo), without anybody knowing what that are assigned to, to determine safety and efficacy of different dose regimens of Evinacumab in patients with persistent high cholesterol despite taking the maximum tolerated lipid modifying therapy

A.4.1

Sponsor's protocol code number

R1500-CL-1643

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03175367

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Regeneron Pharmaceuticals, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Regeneron Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Regeneron Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	777 Old Saw Mill River Road
B.5.3.2	Town/ city	Tarrytown, NY
B.5.3.3	Post code	10591
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@regeneron.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Evinacumab (REGN1500) 3ml vial
D.3.2	Product code	REGN1500
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Evinacumab
D.3.9.1	CAS number	1446419-85-7
D.3.9.2	Current sponsor code	REGN1500
D.3.9.3	Other descriptive name	EVINACUMAB
D.3.9.4	EV Substance Code	SUB181899
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Evinacumab (REGN1500) 20ml vial
D.3.2	Product code	REGN1500
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Evinacumab
D.3.9.1	CAS number	1446419-85-7
D.3.9.2	Current sponsor code	REGN1500
D.3.9.3	Other descriptive name	EVINACUMAB
D.3.9.4	EV Substance Code	SUB181899
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Persistent Hypercholesterolemia Despite Maximally Tolerated Lipid Modifying Therapy

E.1.1.1

Medical condition in easily understood language

Hypercholesterolemia, also called dyslipidemia, is the presence of high
levels of cholesterol in the blood, despite previous and concomitant treatment with Maximally Tolerated Lipid Modifying Therapy

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10020604
E.1.2	Term	Hypercholesterolemia
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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 LDL-C ≥ 100 mg/dL (2.59 mmol/L), despite maximally tolerated statin and PCSK9 inhibitor antibody therapy.

E.2.2

Secondary objectives of the trial

• To evaluate the dose-response effect of evinacumab on other lipid parameters (ie, ApoB, non-high-density lipoprotein cholesterol [non-HDL-C], total cholesterol [TC], Lp (a), triglycerides [TGs], ApoA1, ApoCIII), and total ANGPTL3 in patients with primary hypercholesterolemia
• To evaluate the safety and tolerability of SC and IV doses of evinacumab in patients with primary hypercholesterolemia
• To assess systemic serum concentrations of evinacumab in patients with primary hypercholesterolemia
• To evaluate the potential development of anti-evinacumab antibodies

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

An optional genomic sub-study will be conducted to identify genomic associations with clinical or biomarker response, other clinical outcome measures and possible AEs.
Title : Genomic sub-study optional.
Version and date: R1500-CL-1643.01, 22Jun2017
Objectives: The purpose of the pharmacogenomic analyses is to identify genomic associations with clinical or biomarker response, other clinical outcome measures and possible AEs. In addition, associations between genomic variants and prognosis or progression of as well as other diseases may also be studied. These data may be used or combined with data collected from other studies to identify and validate genomic markers related to the study drug or and other diseases. Analyses may include sequence determination or single nucleotide polymorphism studies of candidate genes and surrounding genomic regions. Other methods, including whole exome sequencing, whole-genome sequencing, DNA copy number variation. The list of methods may be expanded to include novel methodology that may be developed during the course of this study or sample storage period.

E.3

Principal 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

E.4

Principal 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):
- 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
- Positive test for Hepatitis B surface antigen and/or Hepatitis C
antibody (associated with a positive HCV ribonucleic acid [RNA]
polymerase chain reaction)
- Positive serum beta-human chorionic gonadotropin or urine pregnancy
test in women of childbearing potential
- Estimated glomerular filtration rate < 30 mL/min/1.73 m^2
- TSH > 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >
2 x ULN
- Creatine phosphokinase (CPK) > 3 x ULN at screening (1 repeat lab is
allowed)
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 IIIV)
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

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Week 16

E.5.2

Secondary end point(s)

• Percent change in ApoB from baseline to week 16
• Percent change in non-HDL-C from baseline to week 16
• Percent change in TC from baseline to week 16
• Proportion of patients with ≥ 30% reduction in calculated LDL-C at week 16
• Proportion of patients with ≥ 50% reduction in calculated LDL-C at week 16
• Percent change in TGs from baseline to week 16
• Percent change in Lp(a) from baseline to week 16
• Proportion of patients with calculated LDL-C < 100 mg/dL (2.59 mmol/L) at week 16
• Proportion of patients with calculated LDL-C < 70 mg/dL (1.181 mmol/L) at week 16
• Percent change in calculated LDL-C, ApoB, non-HDL-C, TC, TG, and Lp(a) from baseline to week 24 (only applicable to those patients receiving IV route of study treatment administration)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline and Week 16 for all endpoints except last endpoint regarding the Percent change in calculated LDL-C, ApoB, non-HDL-C, TC, TG, and Lp(a) that will be calculated on Baseline and week 24

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

dose ranging study to assess varying doses of SC and IV regimens

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Canada

Czechia

Denmark

Israel

Italy

Netherlands

New Zealand

Norway

Poland

Russian Federation

South Africa

Spain

Sweden

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

152

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

114

F.4.2.2

In the whole clinical trial

252

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All patients who successfully complete this study have the opportunity to enroll in a separate open-label extension study. All patients that enroll in the separate open-label extension study will continue to receive evinacumab.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-04-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-08-30

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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