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

Nephrotic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03004001
• Other study ID #: VA16-029
• Status: Terminated
• Phase: Phase 2
• Start date: January 2017
• Est. completion date: December 2019

Study information

• Verified date: August 2022
• Source: Dallas VA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyslipidemias
• Nephrosis
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Alirocumab
150 mg biweekly
• Alirocumab placebo
placebo
• Atorvastatin
20 mg/day

Locations

Country	Name	City	State
United States	DallasVAMC	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Gloria Vega	Aventis Pharmaceuticals, Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Levels of plasma lipoproteins	ion mobility lipoprotein analysis	up to 10 months
Secondary	Levels of PCSK9	immunoassay	up to 10 months
Secondary	Triglyceride-rich lipoproteins (Remnants)	immunoassay	up to 10 months
Secondary	Lipidomics	mass spectroscopy	up to 10 months