- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03811223
Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia (EVOLVE-FD)
January 17, 2019 updated by: dr.Frank L.J. Visseren, UMC Utrecht
A Multicenter, Randomized, Double-blind, Placebo-controlled, Crossover Trial to Evaluate the Effects of Evolocumab Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia
Patients with familial dysbetalipoproteinemia (FD) have increased triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), beta VLDL, premature atherosclerosis and cardiovascular disease.
They also have a delayed postprandial triglyceride and chylomicron (CM) remnant clearance.
Postprandial hypertriglyceridemia is associated with increased vascular risk.
Although combination therapy with statin and fibrate is recommended in the treatment of patients with FD, there is still a substantial amount of patient who do not reach their treatment target with this medication.
Furthermore no information is available about the postprandial effects of adding evocolumab to standard lipid lowering therapy in FD patients.
Study Overview
Status
Unknown
Intervention / Treatment
Detailed Description
See brief summary
Study Type
Interventional
Enrollment (Anticipated)
30
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Frank LJ Visseren, prof
- Phone Number: +31 88 7557324
- Email: f.l.j.visseren@umcutrecht.nl
Study Contact Backup
- Name: Britt E Heidemann, MD
- Phone Number: +31 88 75 579 94
- Email: b.e.heidemann@umcutrecht.nl
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
Patients diagnosed with Familial Dysbetalipoproteinemia;
- ε2ε2 genotype or dominant APOE mutation genotype (confirmed by genotyping or isoelectric focusing) with any lipid-lowering treatment at a stable dose for at least three months and non-HDL-C >1.6 mmol/L or;
- Patients with ε2ε2 genotype or dominant APOE mutation (confirmed by genotyping or isoelectric focusing) without lipid-lowering treatment and with an ApoB/TC ratio < 0.15.
- >18 years old (on the day of signing informed consent).
Women are postmenopausal and not receiving hormone therapy (including cyclic and non-cyclical hormone replacement therapy or any estrogen antagonist/agonist). Postmenopausal status is defined as:
- no menses for ≥3 years or;
- no menses for ≥1 year but <3 years and confirmed by FSH levels elevated into the postmenopausal range (15-150 IU/L).
- Willingness to maintain a stable diet for the duration of the study.
- Understanding of the study procedures, alternative treatments available, and risks involved with the study and voluntarily agreement to participate by giving written informed consent.
Exclusion criteria:
- Intolerance, known allergy or hypersensitivity to evolocumab (or other PCSK-9 monoclonal antibodies), latex or any of the components of the medication.
- Current or prior exposure to evolocumab or another PCSK9-inhibitor mAb in the past 12 weeks.
- Unable or unwilling to drink an oral fat load.
- Premenopausal women.
- Uncontrolled diabetes as defined by a HbA1c >69 mmol/mol.
- BMI >40 kg/m2.
- Uncontrolled blood pressure with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg.
- Increased hepatic enzymes, defined as alanine transaminase (ALAT) or aspartate transaminase (ASAT) >3 times the ULN, or active liver disease defined as non alcoholic steatohepatitis (NASH), cirrhosis or Child Pugh B and C, or history of chronic active hepatitis B or C; subjects with documented resolution after treatment are permitted.
- Impaired renal function, defined by an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2, and/or need of renal placement therapy or other clinically significant renal disease.
- (Sub)clinical hypothyroidism defined as TSH >5.0 mcl/U/mL or (sub)clinical hyperthyroidism defined as TSH < 0.35 mcl/U/ml.
- Increased levels of creatinine kinase defined as >3 times the ULN.
- Increased fasting levels of triglycerides defined as >10 mmol/L.
- History of organ transplantation and/or use of immunosuppressive medication.
- Use of fish oil or red yeast rice, bempedoic acid, niacin, CETP inhibitors, lomitapide, mipomersen < 6 weeks prior to the study or the use of siRNA targeting PCSK9 inhibitors < 36 weeks prior to the study.
- Active malignancy (<2 year prior to informed consent), except non-melanoma skin cancer or carcinoma in situ of the cervix.
- Known infection with Human Immunodeficiency Virus (HIV) or AIDS.
- Known celiac disease or other disorder associated with significant intestinal malabsorption.
- Known galactose-intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
- Alcohol use, defined as >14 alcoholic consumptions per week for women and >21 alcohol consumptions per week for men. One alcohol consumption unit is defined as follows: 350 mL beer, 150 mL wine or 45 mL alcohol for mixed drinks.
- Current participation or participation in a study with an investigational compound or device within 30 days of signing informed consent.
- Any medical, social or physiological circumstance which interferes the study, based on judgement by the principal investigator.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Evolocumab
Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks
|
Evolocumab 140 mg every 2 weeks for 12 weeks
|
Placebo Comparator: Placebo
Placebo injection once every 2 weeks for 12 weeks
|
Placebo subcutaneous injection every 2 weeks for 12 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
AUC (area under the curve) non-HDL-cholesterol
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Fasting levels, AUC and iAUC of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and ApoB, as well as fasting non-HDL-cholesterol.
Time Frame: 12 weeks
|
12 weeks
|
Percentage change from baseline and absolute difference in fasting and post fat load non-HDL-cholesterol, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and ApoB.
Time Frame: 12 weeks
|
12 weeks
|
Fasting and post fat load lipoprotein (VLDL1, VLDL2, IDL, LDL, HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins).
Time Frame: 12 weeks
|
12 weeks
|
Post fat load ApoB 48-containing lipoprotein concentrations (chylomicrons and chylomicron remnants) and proteins involved in postprandial lipid metabolism.
Time Frame: 12 weeks
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Frank LJ Visseren, prof, UMC Utrecht
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
August 1, 2019
Primary Completion (Anticipated)
January 1, 2021
Study Completion (Anticipated)
March 1, 2021
Study Registration Dates
First Submitted
January 17, 2019
First Submitted That Met QC Criteria
January 17, 2019
First Posted (Actual)
January 22, 2019
Study Record Updates
Last Update Posted (Actual)
January 22, 2019
Last Update Submitted That Met QC Criteria
January 17, 2019
Last Verified
January 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lipid Metabolism Disorders
- Dyslipidemias
- Lipid Metabolism, Inborn Errors
- Hyperlipidemias
- Hyperlipoproteinemias
- Hyperlipoproteinemia Type III
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Evolocumab
Other Study ID Numbers
- UMCU-VASC-CO-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
IPD Plan Description
Currently, there is no plan to make individual participant data available to other researchers, but this is possible in the future.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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