Impact of Evolocumab in Cardiac Transplant Patients With CAV

• ClinicalTrials.gov Identifier: NCT03944577
• Recruitment Status: Recruiting
• First Posted: May 9, 2019
• Last Update Posted: November 4, 2020
• Sponsor: University of Nebraska
• Collaborator: Amgen
• Information provided by (Responsible Party): Douglas Stoller, University of Nebraska

Study Description

Brief Summary:

Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (repatha) is an FDA-approved drug for lowering 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.

Condition or disease	Intervention/treatment	Phase
Heart Transplant	Drug: Evolocumab (Repatha)	Phase 2

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 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients With Coronary Allograft Vasculopathy
• Actual Study Start Date: July 15, 2019
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: March 1, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment Arm; Patients who will receive the study drug.

Drug: Evolocumab (Repatha); 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.

Outcome Measures

Primary Outcome Measures :

1. To measure the effect of evolocumab on serum LDL as measured in mL/dL after 12 weeks of therapy in heart transplant patients. [ Time Frame: 12 weeks ]
   The primary objective of this study is to measure in the impact of PCSK9 inhibition via evolocumab on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline. Change in serum LDL will serve as the primary endpoint for comparison.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

• 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 GFR < 20 ml/min
• Known allergy to evolocumab or its components

Contacts and Locations

Locations

United States, Nebraska

University of Nebraska Medical Center; Recruiting

Omaha, Nebraska, United States, 68198

Contact: Douglas Stoller, MD, PhD 402-559-1350 douglas.stoller@unmc.edu

Sponsors and Collaborators

University of Nebraska

Amgen

More Information

• Responsible Party: Douglas Stoller, Principal Investigator, University of Nebraska
• ClinicalTrials.gov Identifier: NCT03944577
• Other Study ID Numbers: 20177584
• First Posted: May 9, 2019
• Last Update Posted: November 4, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There is not a plan to make individual participant data (IPD) available) to other researchers.

• 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

Keywords provided by Douglas Stoller, University of Nebraska:

coronary allograft vasculopathy; lipid; heart transplant

Additional relevant MeSH terms:

Evolocumab; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents