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

• Sponsor: Gloria Vega (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT03004001
• Collaborator: Regeneron Pharmaceuticals (Industry), Aventis Pharmaceuticals (Industry)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Nephrotic Syndrome	Drug: Alirocumab; Drug: Alirocumab placebo; Drug: Atorvastatin	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
• Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 1, 2019

Arms and Interventions

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: Alirocumab placebo; placebo; Other Names: Praluent placebo ; Drug: Atorvastatin; 20 mg/day; Other Names: Lipitor

Outcome Measures

Primary Outcome Measures

1. Levels of plasma lipoproteins [up to 10 months]

   ion mobility lipoprotein analysis

Secondary Outcome Measures

1. Levels of PCSK9 [up to 10 months]

   immunoassay

2. Triglyceride-rich lipoproteins (Remnants) [up to 10 months]

   immunoassay

3. Lipidomics [up to 10 months]

   mass spectroscopy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DallasVAMC	Dallas	Texas	United States	75216

Sponsors and Collaborators

• Gloria Vega
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Gloria Vega, Principal Investigator at Dallas VA Medical Center, Dallas VA Medical Center
• ClinicalTrials.gov Identifier: NCT03004001
• Other Study ID Numbers: VA16-029
• First Posted: Dec 28, 2016
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Keywords provided by Gloria Vega, Principal Investigator at Dallas VA Medical Center, Dallas VA Medical Center: Severe proteinuria; Dyslipidemia
• Additional relevant MeSH terms: Nephrotic Syndrome; Nephrosis; Dyslipidemias; Syndrome; Atorvastatin; Antibodies, Monoclonal

Study Results

No Results Posted as of Aug 19, 2022