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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03399786




Registration number
NCT03399786
Ethics application status
Date submitted
8/01/2018
Date registered
16/01/2018
Date last updated
18/05/2021

Titles & IDs
Public title
Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
Secondary ID [1] 0 0
2017-001388-19
Secondary ID [2] 0 0
R1500-CL-1629
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Homozygous Familial Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - evinacumab
Treatment: Drugs - Placebo

Experimental: evinacumab -

Experimental: Placebo -


Treatment: Drugs: evinacumab
IV administration of evinacumab

Treatment: Drugs: Placebo
IV administration of placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
Percentage of Participants With =30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
Timepoint [4] 0 0
At Week 24
Secondary outcome [5] 0 0
Percentage of Participants With =50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
Timepoint [5] 0 0
At Week 24
Secondary outcome [6] 0 0
Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)
Timepoint [6] 0 0
Week 24
Secondary outcome [7] 0 0
Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
Timepoint [7] 0 0
At Week 24
Secondary outcome [8] 0 0
Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand)
Timepoint [8] 0 0
At Week 24
Secondary outcome [9] 0 0
Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
Timepoint [9] 0 0
At Week 24
Secondary outcome [10] 0 0
Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)
Timepoint [10] 0 0
At Week 24
Secondary outcome [11] 0 0
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)
Timepoint [11] 0 0
Week 24
Secondary outcome [12] 0 0
Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
Timepoint [13] 0 0
Week 24
Secondary outcome [14] 0 0
Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
Timepoint [14] 0 0
Week 24
Secondary outcome [15] 0 0
Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
Timepoint [15] 0 0
Week 24
Secondary outcome [16] 0 0
Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand)
Timepoint [16] 0 0
Week 24

Eligibility
Key inclusion criteria
Key

1. Diagnosis of functional HoFH
2. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks
3. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study

Key
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit
2. Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been stable before the screening visit
3. Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
4. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit
5. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled (HbA1c >9%) diabetes
7. History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
8. Pregnant or breastfeeding women
9. Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug
10. Men who are sexually active with women of child bearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period and for 24 weeks after the last dose of study drug regardless of vasectomy status

Note: Other protocol defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/03/2020
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Regeneron Research Site - Camperdown
Recruitment hospital [2] 0 0
Regeneron Research Site - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Austria
State/province [7] 0 0
Innsbruck
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
France
State/province [9] 0 0
Cedex
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
Greece
State/province [11] 0 0
Ioannina
Country [12] 0 0
Greece
State/province [12] 0 0
Athens
Country [13] 0 0
Italy
State/province [13] 0 0
Napoli
Country [14] 0 0
Japan
State/province [14] 0 0
Fukuoka
Country [15] 0 0
Japan
State/province [15] 0 0
Hyogo
Country [16] 0 0
Japan
State/province [16] 0 0
Ishikawa
Country [17] 0 0
Japan
State/province [17] 0 0
Osaka
Country [18] 0 0
Netherlands
State/province [18] 0 0
Amsterdam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Rotterdam
Country [20] 0 0
South Africa
State/province [20] 0 0
Johannesburg
Country [21] 0 0
Ukraine
State/province [21] 0 0
Ivano-Frankivs'k
Country [22] 0 0
Ukraine
State/province [22] 0 0
Kharkiv
Country [23] 0 0
Ukraine
State/province [23] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab intravenously (IV) in comparison to placebo after 24 weeks in patients with homozygous familial hypercholesterolemia (HoFH). The secondary objectives of the study are to evaluate the effect of evinacumab IV on other lipid parameters, evaluate the effect of evinacumab on LDL-C goal attainment, assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria), evaluate the safety and tolerability of evinacumab in patients with HoFH, assess the pharmacokinetics (PK) of evinacumab in patients with HoFH and evaluate the potential development of anti-evinacumab antibodies.
Trial website
https://clinicaltrials.gov/study/NCT03399786
Trial related presentations / publications
Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03399786