Evolocumab In Advanced Chronic Kidney Disease Trial

NCT04510844 | Withdrawn Phase 4 DMC FDA Drug

• 2 other identifiers: 20-0040521-00455
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Kidney Diseases; High Cholesterol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Serious Adverse Events (SAEs)

  Baseline, Week 52

• Change in coronary flow reserve (CFR)

  Baseline, Week 52

Study Arms (2)

Study Drug Group

EXPERIMENTAL

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

Drug: Evolocumab

Placebo group

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Evolocumab 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.

Study Drug Group

Placebo 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.

Placebo group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (2)

NYU Langone Nephrology Associates - Long Island

Mineola, New York, 11501, United States

Location

NYU Langone Health

New York, New York, 10010, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• David Charytan, MD

  NYULangone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: August 12, 2020
• Study Start: March 1, 2021
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (2)