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

Primary Purpose

Nephrotic Syndrome

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Alirocumab

Alirocumab placebo

Atorvastatin

About this trial

This is an interventional treatment trial for Nephrotic Syndrome focused on measuring Severe proteinuria, Dyslipidemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

DallasVAMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Alirocumab and atorvastatin

Alirocumab placebo and atorvastatin

Arm Description

Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d

Alirocumab placebo biweekly and atorvastatin 20 mg/d

Outcomes

Primary Outcome Measures

Levels of plasma lipoproteins

ion mobility lipoprotein analysis

Secondary Outcome Measures

Levels of PCSK9

immunoassay

Triglyceride-rich lipoproteins (Remnants)

immunoassay

Lipidomics

mass spectroscopy

Full Information

NCT ID

NCT03004001

First Posted

December 16, 2016

Last Updated

August 17, 2022

Sponsor

Gloria Vega

Collaborators

Regeneron Pharmaceuticals, Aventis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03004001

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Terminated

Why Stopped

Difficult recruitment

Study Start Date

January 2017 (undefined)

Primary Completion Date

December 2019 (Actual)

Study Completion Date

December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Gloria Vega

Collaborators

Regeneron Pharmaceuticals, Aventis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nephrotic Syndrome

Keywords

Severe proteinuria, Dyslipidemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alirocumab and atorvastatin

Arm Type

Experimental

Arm Description

Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d

Arm Title

Alirocumab placebo and atorvastatin

Arm Type

Placebo Comparator

Arm Description

Alirocumab placebo biweekly and atorvastatin 20 mg/d

Intervention Type

Drug

Intervention Name(s)

Alirocumab

Other Intervention Name(s)

Praluent

Intervention Description

150 mg biweekly

Intervention Type

Drug

Intervention Name(s)

Alirocumab placebo

Other Intervention Name(s)

Praluent placebo

Intervention Description

placebo

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Other Intervention Name(s)

Lipitor

Intervention Description

20 mg/day

Primary Outcome Measure Information:

Title

Levels of plasma lipoproteins

Description

ion mobility lipoprotein analysis

Time Frame

up to 10 months

Secondary Outcome Measure Information:

Title

Levels of PCSK9

Description

immunoassay

Time Frame

up to 10 months

Title

Triglyceride-rich lipoproteins (Remnants)

Description

immunoassay

Time Frame

up to 10 months

Title

Lipidomics

Description

mass spectroscopy

Time Frame

up to 10 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gloria L Vega, PhD

Organizational Affiliation

Dallas VAMC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yin Oo, MD

Organizational Affiliation

Dallas VA Medical Center

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Michael Concepcion, MD

Organizational Affiliation

Dallas VA Medical Center

Official's Role

Study Director

Facility Information:

Facility Name

DallasVAMC

City

Dallas

State/Province

Texas

ZIP/Postal Code

75216

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

3165483

Citation

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.

Results Reference

background

PubMed Identifier

10644862

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. doi: 10.1159/000013549.

Results Reference

background

PubMed Identifier

7723244

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. doi: 10.1038/ki.1995.73.

Results Reference

background

PubMed Identifier

24315769

Citation

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.

Results Reference

background

Learn more about this trial

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

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