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.

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. - EVOLVE-FD

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON49866

Enrollment

Registered

2019-08-01

Start date

2019-10-29

Completion date

Unknown

Last updated

2025-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Familial Dysbetalipoproteinemia Fredrickson Type III hyperlipoproteinemia

Interventions

Evolocumab 140 mg subcutaneous every 2 weeks

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: 1. Subjects diagnosed with Familial Dysbetalipoproteinemia; defined as; *known *2*2 genotype or known dominant APOE mutation genotype (confirmed by genotyping or isoelectric focusing) and a phenotype of familial dysbetalipoproteinemia (defined as an ApoB/TC ratio 5 mmol/L and TG > 3 mmol/L or non-HDL-c/ApoB ratio > 6.55 mmol/g; with or without medication. 2. If using any lipid lowering treatment: dose must be stable for at least three months with non-HDL-C levels > 1.6 mmol/L. 3. >=18 or ==3 years or; *no menses for >=1 year but

Exclusion criteria

Exclusion criteria: 1. Intolerance, known allergy or hypersensitivity to evolocumab (or other PCSK-9 monoclonal antibodies), latex or any of the components of the medication. 2. Current or prior exposure ((69 mmol/mol. 6. BMI >40 kg/m2. 7. Uncontrolled blood pressure with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg. 8. 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. 9. Impaired renal function, defined by an estimated glomerular filtration rate (eGFR) 5.0 mcl/U/mL or (sub)clinical hyperthyroidism defined as TSH 3 times the ULN. 12. Increased fasting levels of triglycerides defined as >10 mmol/L. 13. History of organ transplantation. 14. Current use or use in the past 3 months of immunosuppressive medication. 15. Use of fish oil or red yeast rice, bempedoic acid, niacin, CETP inhibitors, lomitapide, mipomersen 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. 21. Current participation or participation in a study with an investigational compound or device within 30 days of signing informed consent. 22. Any medical, social or physiological circumstance which interferes the study, based on judgement by the principal investigator.

Design outcomes

Primary

Measure	Time frame
The primary endpoint is non-HDL-C AUC (area under the curve).	—

Secondary

Measure	Time frame
1. Fasting, post fat load AUC and iAUC of total cholesterol (TC), LDL-C (directly measured), HDL-C, TG, ApoB and Lp(a); as well as fasting non-HDL-C after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in subjects with FD on standard lipid-lowering therapy. 2. Percentage change and absolute change from baseline in fasting and post fat load AUC and iAUC of non-HDL-c, TC, LDL-C (directly measured), HDL-C, TG, ApoB and Lp(a) after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in subjects with FD on standard lipid-lowering therapy. 3. Fasting and post fat load AUC and iAUC of lipoprotein (CM, VLDL, IDL, LDL and HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins) and metabolic parameters after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in patients with FD on standard lipid-lowering therapy. 4. Post fat load AUC and iAUC of ApoB48-containing lipoprotein concentrations (chylomicrons, chylomicron remnants) after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in patients with FD on standard lipid-lowering therapy. 5. Occurrence of adverse events after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placbo in subjects with FD on standard lipid-lowering therapy.	—

Measure

Time frame

1. Fasting, post fat load AUC and iAUC of total cholesterol (TC), LDL-C (directly measured), HDL-C, TG, ApoB and Lp(a); as well as fasting non-HDL-C after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in subjects with FD on standard lipid-lowering therapy. 2. Percentage change and absolute change from baseline in fasting and post fat load AUC and iAUC of non-HDL-c, TC, LDL-C (directly measured), HDL-C, TG, ApoB and Lp(a) after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in subjects with FD on standard lipid-lowering therapy. 3. Fasting and post fat load AUC and iAUC of lipoprotein (CM, VLDL, IDL, LDL and HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins) and metabolic parameters after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in patients with FD on standard lipid-lowering therapy. 4. Post fat load AUC and iAUC of ApoB48-containing lipoprotein concentrations (chylomicrons, chylomicron remnants) after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placebo in patients with FD on standard lipid-lowering therapy. 5. Occurrence of adverse events after 12 weeks treatment with subcutaneous evolocumab (140 mg pre-filled pen every 2 weeks) compared to placbo in subjects with FD on standard lipid-lowering therapy.

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)