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

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.

Study Overview

• Status: Terminated
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Alirocumab; Drug: Atorvastatin; Drug: Alirocumab placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75216
      • DallasVAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gloria Vega
• Collaborators: Regeneron Pharmaceuticals; Aventis Pharmaceuticals
• Investigators: Principal Investigator: Gloria L Vega, PhD, Dallas VAMC; Study Director: Yin Oo, MD, Dallas VA Medical Center; Study Director: Michael Concepcion, MD, Dallas VA Medical Center

Publications and helpful links

General Publications

• Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. doi: 10.1038/ki.1988.125.
• Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7. doi: 10.1159/000013549.
• Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int. 1995 Feb;47(2):579-86. doi: 10.1038/ki.1995.73.
• Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (Estimate): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Dyslipidemia; Severe proteinuria
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Disease; Lipid Metabolism Disorders; Syndrome; Dyslipidemias; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Antibodies, Monoclonal
• Other Study ID Numbers: VA16-029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No