Evolocumab In Advanced Chronic Kidney Disease Trial

NCT ID: NCT04510844

Last Updated: 2022-07-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2021-10-01

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.

Conditions

Chronic Kidney Diseases; High Cholesterol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Study Drug Group

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

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: DRUG

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.

Placebo group

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Charytan, MD

Role: PRINCIPAL_INVESTIGATOR

NYULangone Health

Locations

NYU Langone Nephrology Associates - Long Island

Mineola, New York, United States

NYU Langone Health

New York, New York, United States

Countries

United States

Other Identifiers

21-00455

Identifier Type: OTHER

Identifier Source: secondary_id

20-00405

Identifier Type: -

Identifier Source: org_study_id