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

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03321656
• Other study ID #: 42753
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 28, 2019
• Est. completion date: March 31, 2026

Study information

• Verified date: March 2024
• Source: University of Kentucky
• Contact: Deepa Valvi, DrPH
• Phone: 8592579443
• Email: deepa.valvi[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

Drug:
• Tacrolimus
0.1-0.2 mg/kg/day orally divided into two doses every 12 hours orally
• Envarsus XR
0.07-0.14 mg/kg/day every morning orally

Locations

Country	Name	City	State
United States	Deepa Valvi	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Roberto Gedaly	Veloxis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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	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