Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome

Study Overview
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Brief Summary
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The study purpose is to determine the hypolipidemic effect of Alirocumab co-administered with atorvastatin on levels of triglyceride-rich lipoproteins and LDL compared to monotherapy with atorvastatin in patients with dyslipidemia secondary to nephrotic syndrome.

Detailed Description
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The trial is randomized (1:1 alirocumab to placebo), double-blinded, placebo-controlled with a cross-over design. The trial will last 10 months and includes a 10 week washout period between study phases.Twenty adult subjects with dyslipidemia secondary to nephrotic syndrome and treated with atorvastatin will be recruited. Alirocumab or placebo will be co-administered biweekly. Safety, efficacy chemistries, vital signs, anthropometry and monitoring for adverse events also will done at each visit.

Official Title
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Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome

Conditions
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Nephrotic Syndrome

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Alirocumab placebo
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nephrotic Syndrome (NS) (FSGS, IMN or NS and type 2 DM) atorvastatin LDL C >= 70 mg/dl or non-HDL C >= 100 mg/dl Plasma trigycerides < 800 mg/dl. Highly effective methods of contraception for pre-menopausal women Post-menopausal women must be amenorrheic for at least 12 months. Exclusion Criteria: homozygous FH Fibrates within 6 weeks of screening visit Uncontrolled hypothyroidism Known history of hemorrhagic stroke Known history of loss of function of PCSK9 use of systemic corticosteroids unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks of randomization Previous treatment with at least a single dose of alirocumab or any other anti-PCSK9 monoclonal antibody Other conditions or situations per protocol Laboratory findings or contraindications to background therapies Warnings/precautions of use (when appropriate) as displayed in the respective national product labeling Any currently known contra-indication to study drug, pregnancy or breastfeeding of infants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alirocumab and atorvastatin<br>Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d | Drug: Alirocumab<br>* 150 mg biweekly<br>* Other names: Praluent;Drug: Atorvastatin<br>* 20 mg/day<br>* Other names: Lipitor;|
| Placebo Comparator: Alirocumab placebo and atorvastatin<br>Alirocumab placebo biweekly and atorvastatin 20 mg/d | Drug: Alirocumab placebo<br>* placebo<br>* Other names: Praluent placebo;Drug: Atorvastatin<br>* 20 mg/day<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of plasma lipoproteins | ion mobility lipoprotein analysis | up to 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of PCSK9 | immunoassay | up to 10 months | 
| Triglyceride-rich lipoproteins (Remnants) | immunoassay | up to 10 months | 
| Lipidomics | mass spectroscopy | up to 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe proteinuria, Dyslipidemia