Impact of Envarsus XR® on Kidney Biopsy Subclinical Rejection and Blood Immunologic Profile

This will be a single center, prospective, open-label, randomized, controlled trial comparing Envarsus XR® to twice-daily tacrolimus. The targeted population will be patients with end stage renal disease listed for primary solitary kidney transplant. Transplant Surgery is not part of the study.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Tacrolimus; Drug: Envarsus XR

Detailed Description

Participants will be identified through the Department of Transplantation Surgery at the University of Kentucky. Participants will be pre-screened by the department for entry into the study. The investigator will determine if the participant meets study eligibility requirements.

The purpose of this research is to gather information on how safe and effective of Envarsus® is when compared to twice-daily tacrolimus. The results of this study will be shared with the company providing financial support for the study, the Food and Drug Administration and other federal agencies, if required.

All participants that successfully meeting inclusion criteria will be randomized (like the flipping of coin) to Envarsus vs. Tacrolimus at the time of transplant.

Participants will be randomized to one of two treatment arms. Treatment begins on post-op day 1.

• Treatment: Envarsus® 0.07-0.14 mg/kg/day every morning
• Control: Generic tacrolimus 0.1-0.2 mg/kg/day in 2 divided doses given every 12 hours

The total amount of time a person will be asked to volunteer for this study is 9-18 hours over the next 6 months.

Participants will need to complete 9 study visits each of these visits will take approximately 1-2 hours to complete. Participants will be given medication dosing diaries to complete throughout the study and will undergo 2 kidney biopsies.

Participants will be screened for HIV, Hepatitis B and Hepatitis C viruses.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Deepa Valvi, DrPH; Phone Number: 8592579443; Email: deepa.valvi@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Deepa Valvi
      • Principal Investigator: Roberto Gedaly, MD
      • Sub-Investigator: TrisAnn Rendulic, PharmD
      • Contact: Deepa Valvi, DrPH; Phone Number: 859-257-9443; Email: deepa.valvi@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fluent in English able to understand and provide informed consent.
• End stage renal disease listed for primary solitary kidney transplant.
• Willing to participate in the study and comply with study requirements as evidenced by signed IRB-approved informed consent.
• Female who are of childbearing potential will be asked to use 2 different medically acceptable methods of contraception for the duration of the study and at least 1 year post-infusion.

Exclusion Criteria:

• Previously undergone organ, tissue or cell transplant
• Allergic to Tacrolimus or MMF (Cellcept)
• Chronic use of blood thinners
• Previous chronic use of glucocorticoids or other immunosuppression, or biologic immunomodulators (prescribed for the treatment of serious inflammatory disorders)
• Significant or active infection
• Diagnosed with HIV, Hepatitis B or C, Herpes simplex virus, Varicella-Zoster virus, Epstein-Barr virus
• Have or have had cancer with in the past 3 years
• Have taken part in another study that involved an investigational drug within the last 12 months.
• Have a history of delayed or abnormal wound healing
• Are pregnant or breastfeeding
• Had a transfusion within the past 3 months
• Have or plan to be receive a live vaccination (intranasal influenza measles, mumps, rubella, oral polio, yellow fever, varicella)
• Are unable or unwilling to comply with study protocol or procedures.
• Current use anticoagulation medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tacrolimus; 0.1 - 0.2 mg/kg/day in 2 divided doses every 12 hours orally	Drug: Tacrolimus; 0.1-0.2 mg/kg/day orally divided into two doses every 12 hours orally
Experimental: Envarsus XR; 0.07-0.14 mg/kg/day every morning orally	Drug: Envarsus XR; 0.07-0.14 mg/kg/day every morning orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Change in the percentage of donor specific antibodies	We will check these donor specific antibodies to: HLA-A, -B and -C; or HLA-DR, -DQ and -DP. We will quantify the expression of these markers by Flow Cytometry analysis and reported as mean fluorescence intensity (MFI) units.	Time of transplant and six months post-transplant
Changes in the percentage of blood immunologic markers	We will monitor the lymphocyte profile in blood in response to these 2 different treatments. The lymphocyte profile test will be performed by multi-parametric flow cytometry analysis with a panel of specific flourochrome-conjugated antibodies to selectively determine the following sub-populations: Circulating T cells: CD4/CD8 rates and determine the following CD4 subpopulations: effector TH1, TH2, TH9, Tfh, and regulatory/suppressor T cells.; Circulating B cells (number and percentage of naïve, activated, memory and plasma B cells.; Circulating NK cells (mature and immature)	Time of transplant and six months post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in creatinine clearance	Baseline creatinine will be considered the creatinine plasma levels several days after transplantation once the kidney function is stabilized.	Time of transplant and six months post-transplant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in GFR	We will use the MDRD GFR equation to estimate glomerular filtration rate based on baseline creatinine and patient characteristics (age, gender and race)	30 Days post transplant and months 3 and 6

Collaborators and Investigators

• Sponsor: Roberto Gedaly
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Roberto Gedaly, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 42753

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No