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Evolocumab In Advanced Chronic Kidney Disease Trial (EVO-CKD)

Primary Purpose

Chronic Kidney Diseases, High Cholesterol

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Evolocumab

Placebo

About this trial

This is an interventional treatment trial for Chronic Kidney Diseases

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

CKD Stage 4-5 defined as
- eGFR ≤30 mL/min/1.73m2 on screening lab OR
- Treatment with maintenance hemodialysis for at least 30 days prior to screening
LDL ≥70 mg/dL and
- Treatment with maximal tolerated doses of a statin OR
- Statin intolerance defined as any history of intolerance or allergy to ≥1 statin
Age 40-80 years
- Individuals ≤60 years old are required to have ≥1 of the following cardiovascular risk factors:
  - History of CV disease
  - History of peripheral vascular disease
  - Diabetes
  - Smoking
  - Baseline LDL ≥160 mg/dL
  - Macroalbuminuria (albumin to creatinine ratio ≥300 mg/g on spot sample)

Exclusion Criteria:

Age >80 years
Expected survival < 1 year
Transplant expected within < 1 year
Active liver disease (history of cirrhosis, ALT or AST > 2x ULN)
CPK > 5x ULN at screening
Malignancy within 5 years except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma
Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period
Currently enrolled in another interventional study
Female subject who has not used at least (1) effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal.
- Effective measures of birth control include surgical sterilization, barrier methods, hormonal contraceptives and intrauterine devices.
Pregnant or breast-feeding subjects
Known sensitivity or intolerance to study medications

The following additional criteria will be utilized to exclude individuals from participating in the PET substudy:

Severe asthma or obstructive lung disease defined by
- Hospitalization for asthma or obstructive lung disease within 8 weeks
- Use of oral steroids for lung disease within 8 weeks
- Chronic oxygen therapy
- Use of rescue inhalers ≥three times weekly in the previous 4 weeks
History of seizures
Second or third-degree AV block, unless a functioning pacemaker is present
Sinus node dysfunction unless a functioning pacemaker is present

Sites / Locations

NYU Langone Nephrology Associates - Long Island
NYU Langone Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Study Drug Group

Placebo group

Arm Description

Participants who will receive a shot of the Evolocumab at Visit 3 and self-administer the rest of the shots at visit 4-7.

Participants who will receive a Placebo shot at Visit 3 and self-administer the rest of the shots at visit 4-7.

Outcomes

Primary Outcome Measures

Absolute change in LDL cholesterol concentration

The primary endpoint is selected to evaluate the key pharmacologic mechanism underlying Evolocumab's cardiovascular benefits. This will be analyzed with Lipid parameters.

Secondary Outcome Measures

Number of Serious Adverse Events (SAEs)

Change in coronary flow reserve (CFR)

Change in coronary flow reserve (CFR), the key secondary efficacy endpoint, is a measure of overall cardiovascular health.This test provides an integrative measure of myocardial microvascular supply and myocardial endothelial function as well as large vessel coronary flow. Change in coronary flow reserve over one year as measured by cardiac PET scanning.

Full Information

NCT ID

NCT04510844

First Posted

June 30, 2020

Last Updated

July 27, 2022

Sponsor

NYU Langone Health

1. Study Identification

Unique Protocol Identification Number

NCT04510844

Brief Title

Evolocumab In Advanced Chronic Kidney Disease Trial

Acronym

EVO-CKD

Official Title

A Phase IV, Double-Blind, Placebo-Controlled, Multi-Center Trial To Study The Effects Of Evolocumab In Stage IV-V Chronic Kidney Disease: The Cardiovascular and Lipid-Lowering Effects Of Evolocumab In Advanced Chronic Kidney Disease Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Withdrawn

Why Stopped

loss of funding

Study Start Date

March 1, 2021 (Actual)

Primary Completion Date

October 1, 2021 (Actual)

Study Completion Date

October 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NYU Langone Health

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.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

110 individuals with stage 4-5 Chronic Kidney Disease (CKD) will be randomized to 1-year of blinded Evolocumab or placebo. Subjects will undergo evaluation of circulating lipids at baseline and end of study. A substudy including 50 subjects will assess myocardial rest and stress positron emission tomography (PET) at baseline and at 1-year.

Detailed Description

The purpose of this study is to evaluate the effect of evolocumab (Repatha®)-a Food and Drug Administration (FDA)-approved biological drug that has been shown to reduce LDL cholesterol (bad cholesterol) Early data show that the beneftis of evolocumab may be increased as kidney function declines. This trial is therefore designed to provide additional evidence regarding the safety and cholesterol-lowering effects of evolocumab compared with placebo, a pill that has no therapeutic effect, in advanced CKD patients.

6. Conditions and Keywords

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

Chronic Kidney Diseases, High Cholesterol

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study Drug Group

Arm Type

Experimental

Arm Description

Participants who will receive a shot of the Evolocumab at Visit 3 and self-administer the rest of the shots at visit 4-7.

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Participants who will receive a Placebo shot at Visit 3 and self-administer the rest of the shots at visit 4-7.

Intervention Type

Drug

Intervention Name(s)

Evolocumab

Intervention Description

Evolocumab is commercially available in the United States and is manufactured by Amgen. Drug and placebo, will be supplied by the manufacturer. The SureClick® pre-filled auto injector contain Evolocumab (140 mg) acetate (1.2 mg), polysorbate 80 (0.1 mg), proline (25 mg) in water for Injection. Evolocumab will be administered at a dose of 420 mg subcutaneously once monthly.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo will be supplied by the manufacturer. Placebo auto injectors will be identically packaged but will lack the active ingredient. Placebo will be administered at an equivalent volume to Evolocumab and given subcutaneously once monthly.

Primary Outcome Measure Information:

Title

Absolute change in LDL cholesterol concentration

Description

The primary endpoint is selected to evaluate the key pharmacologic mechanism underlying Evolocumab's cardiovascular benefits. This will be analyzed with Lipid parameters.

Time Frame

Baseline, Week 52

Secondary Outcome Measure Information:

Title

Number of Serious Adverse Events (SAEs)

Time Frame

Baseline, Week 52

Title

Change in coronary flow reserve (CFR)

Description

Time Frame

Baseline, Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: CKD Stage 4-5 defined as eGFR ≤30 mL/min/1.73m2 on screening lab OR Treatment with maintenance hemodialysis for at least 30 days prior to screening LDL ≥70 mg/dL and Treatment with maximal tolerated doses of a statin OR Statin intolerance defined as any history of intolerance or allergy to ≥1 statin Age 40-80 years Individuals ≤60 years old are required to have ≥1 of the following cardiovascular risk factors: History of CV disease History of peripheral vascular disease Diabetes Smoking Baseline LDL ≥160 mg/dL Macroalbuminuria (albumin to creatinine ratio ≥300 mg/g on spot sample) Exclusion Criteria: Age >80 years Expected survival < 1 year Transplant expected within < 1 year Active liver disease (history of cirrhosis, ALT or AST > 2x ULN) CPK > 5x ULN at screening Malignancy within 5 years except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period Currently enrolled in another interventional study Female subject who has not used at least (1) effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal. Effective measures of birth control include surgical sterilization, barrier methods, hormonal contraceptives and intrauterine devices. Pregnant or breast-feeding subjects Known sensitivity or intolerance to study medications The following additional criteria will be utilized to exclude individuals from participating in the PET substudy: Severe asthma or obstructive lung disease defined by Hospitalization for asthma or obstructive lung disease within 8 weeks Use of oral steroids for lung disease within 8 weeks Chronic oxygen therapy Use of rescue inhalers ≥three times weekly in the previous 4 weeks History of seizures Second or third-degree AV block, unless a functioning pacemaker is present Sinus node dysfunction unless a functioning pacemaker is present

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Charytan, MD

Organizational Affiliation

NYULangone Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

NYU Langone Nephrology Associates - Long Island

City

Mineola

State/Province

New York

ZIP/Postal Code

11501

Country

United States

Facility Name

NYU Langone Health

City

New York

State/Province

New York

ZIP/Postal Code

10010

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

IPD Sharing Time Frame

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

IPD Sharing Access Criteria

The investigator who proposed to use the data.Upon reasonable request. Requests should be directed to David.charytan@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Learn more about this trial

Evolocumab In Advanced Chronic Kidney Disease Trial

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