Impact of Evolocumab in Cardiac Transplant Patients With CAV

Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy

Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.

Study Overview

• Status: Completed
• Conditions: Heart Transplant
• Intervention / Treatment: Drug: Evolocumab

Detailed Description

Heart transplant remains the treatment of choice for patients with advanced heart failure. Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of the donor heart, and limits long term survival after transplant. The pathophysiology of CAV is complex and involves smooth muscle proliferation, inflammatory infiltrates, and lipid deposition. To date, only statin therapy has reduced CAV-related mortality. PCSK9 inhibitors are a new lipid lowering therapy shown to reduce cardiovascular clinical events in patients with coronary artery disease. We hypothesize that PCSK9 inhibition via evolocumab will significantly lower low density lipoprotein (LDL) and be well-tolerated in transplant patients with CAV. This phase II, open label, single center trial with enroll up to 40 heart transplant patients with CAV for treatment with evolocumab for one year. The primary outcome will be percent change in LDL at 12 weeks. Secondary outcomes will include change in CAV progression, impact of evolocumab on immunosuppression regimens and transplant rejection, and change in serum lipids after 52 weeks. Results of this study are intended to provide safety data in heart transplant patients with CAV and assess secondary outcomes including CAV progression and impact on immunosuppression and transplant rejection.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Heart transplant patients 19-80 years of age
• Coronary allograft vasculopathy grade 1 or 2 documented by left heart cardiac catheterization
• Able to provide signed informed consent

Exclusion Criteria:

• Cardiac allograft vasculopathy (CAV) grade 3
• Rejection requiring IV therapy in the prior 3 months
• Infection requiring IV therapy in the prior 3 months
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal
• Current or recent use of a PCSK9 inhibitor within the past 12 weeks
• Organ transplant recipient other than heart
• Renal dysfunction defined as glomerular filtration rate (GFR) < 20 ml/min
• Known allergy to evolocumab or its components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Evolocumab; Patients who will receive the study drug.

Drug: Evolocumab; Enrolled study participants will be treated with evolocumab (Repatha) 140 mg injected subcutaneously every 2 weeks for 52 weeks. All study participants will receive instruction on correct self-administration by research pharmacists. Study drug will be mailed to patients on a monthly basis for self-administration by patients. The evolocumab dose (140 mg every 2 weeks) will remain constant for the duration of the study. Side effects will be assessed on a quarterly basis. Serious adverse events considered related to treatment, death, and pregnancy will all result in immediate discontinuation of the study drug.; Other Names: Repatha

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab	The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.	12 weeks

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: Amgen
• Investigators: Principal Investigator: Douglas A Stoller, MD, PhD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: PCSK9; lipid; heart transplant; coronary allograft vasculopathy; low density lipoprotein; proprotein convertase subtilisin/kexin type 9
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; PCSK9 Inhibitors; Evolocumab
• Other Study ID Numbers: 0104-19-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make individual participant data (IPD) available) to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes