Evolocumab In Advanced Chronic Kidney Disease Trial

Chronic Kidney Diseases Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04510844
• Other study ID #: 20-00405
• Secondary ID: 21-00455
• Status: Withdrawn
• Phase: Phase 4
• Start date: March 1, 2021
• Est. completion date: October 1, 2021

Study information

• Verified date: July 2022
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• High Cholesterol
• Hypercholesterolemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Evolocumab
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
United States	NYU Langone Nephrology Associates - Long Island	Mineola	New York
United States	NYU Langone Health	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 52
Secondary	Number of Serious Adverse Events (SAEs)		Baseline, Week 52
Secondary	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.	Baseline, Week 52