Familial DysbetalipoproteinemiaPhase 4EVOLVE-FDNCT03811223
Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia
A Phase 4 study testing Evolocumab Auto-Injector [Repatha] in people with Familial Dysbetalipoproteinemia and Hyperlipoproteinemia Type III, run by UMC Utrecht.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Dysbetalipoproteinemia, Hyperlipoproteinemia Type III
- What is being tested?
- Evolocumab Auto-Injector [Repatha]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Aug 2019to Mar 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read the detailed description
See brief summary
- Being tested
- Evolocumab Auto-Injector [Repatha], Placebos
- Keywords
- Postprandial hyperlipidemia, Evolocumab, PCSK9 monoclonal antibody
- Medical subject headings
- Hyperlipoproteinemia Type III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evolocumab Auto-Injector [Repatha]Drug
Evolocumab 140 mg every 2 weeks for 12 weeks
PlacebosDrug
Also called Placebo
Placebo subcutaneous injection every 2 weeks for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Experimental | Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks Receives: Drug: Evolocumab Auto-Injector [Repatha] |
| Placebo | Placebo comparator | Placebo injection once every 2 weeks for 12 weeks Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC (area under the curve) non-HDL-cholesterol
Measured: 12 weeks
Secondary outcomes (4)
Fasting levels, AUC and iAUC of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and ApoB, as well as fasting non-HDL-cholesterol.
Measured: 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.
Measured: 12 weeks
Fasting and post fat load lipoprotein (VLDL1, VLDL2, IDL, LDL, HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins).
Measured: 12 weeks
Post fat load ApoB 48-containing lipoprotein concentrations (chylomicrons and chylomicron remnants) and proteins involved in postprandial lipid metabolism.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study startAug 2019 (estimated)
- Primary completionJan 2021 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial DysbetalipoproteinemiaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, University Medical Center Nijmegen
- Responsible party
- Principal investigator, dr.Frank L.J. Visseren, UMC Utrecht
- Investigators
- Frank LJ Visseren, prof, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03811223
- Sponsor's protocol ID
- UMCU-VASC-CO-002
- Acronym
- EVOLVE-FD
- Status last verified
- Jan 2019
- First submitted
- 17 Jan 2019
- Last updated
- 22 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Currently, there is no plan to make individual participant data available to other researchers, but this is possible in the future.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03811223
- Acronym / sponsor ID
- EVOLVE-FD / UMCU-VASC-CO-002
- Keywords
- Postprandial hyperlipidemia, Evolocumab, PCSK9 monoclonal antibody
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, University Medical Center Nijmegen
- Study start
- Aug 2019 (estimated)
- Primary completion
- Jan 2021 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 22 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
See brief summary
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Experimental | Drug: Evolocumab Auto-Injector [Repatha]Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks |
| Placebo | Placebo comparator | Drug: PlacebosPlacebo injection once every 2 weeks for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients diagnosed with Familial Dysbetalipoproteinemia;
- >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:
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Evolocumab Auto-Injector [Repatha]Evolocumab 140 mg every 2 weeks for 12 weeks | Drug | Evolocumab |
| PlacebosAlso: PlaceboPlacebo subcutaneous injection every 2 weeks for 12 weeks | Drug | Placebo |
Primary outcome
AUC (area under the curve) non-HDL-cholesterol
Time frame: 12 weeks
4 secondary outcomes
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
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
Fasting and post fat load lipoprotein (VLDL1, VLDL2, IDL, LDL, HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins).
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Individual participant dataSharing planned: Undecided. Currently, there is no plan to make individual participant data available to other researchers, but this is possible in the future.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank LJ Visseren, prof principal investigator
UMC Utrecht
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Evolocumab Auto-Injector [Repatha] in people with Familial Dysbetalipoproteinemia and Hyperlipoproteinemia Type III, run by UMC Utrecht.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Frank LJ Visseren, prof (+31 88 7557324, f.l.j.visseren@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC (area under the curve) non-HDL-cholesterol (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.