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

Primary Purpose

End Stage Renal Disease

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tacrolimus

Envarsus XR

About this trial

This is an interventional treatment trial for End Stage Renal Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Deepa ValviRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Tacrolimus

Envarsus XR

Arm Description

0.1 - 0.2 mg/kg/day in 2 divided doses every 12 hours orally

0.07-0.14 mg/kg/day every morning orally

Outcomes

Primary Outcome Measures

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.

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)

Secondary Outcome Measures

Changes in creatinine clearance

Baseline creatinine will be considered the creatinine plasma levels several days after transplantation once the kidney function is stabilized.

Full Information

NCT ID

NCT03321656

First Posted

September 28, 2017

Last Updated

March 20, 2023

Sponsor

Roberto Gedaly

Collaborators

Veloxis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03321656

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 28, 2019 (Actual)

Primary Completion Date

March 31, 2025 (Anticipated)

Study Completion Date

March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Roberto Gedaly

Collaborators

Veloxis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

End Stage Renal Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tacrolimus

Arm Type

Active Comparator

Arm Description

0.1 - 0.2 mg/kg/day in 2 divided doses every 12 hours orally

Arm Title

Envarsus XR

Arm Type

Experimental

Arm Description

0.07-0.14 mg/kg/day every morning orally

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

0.1-0.2 mg/kg/day orally divided into two doses every 12 hours orally

Intervention Type

Drug

Intervention Name(s)

Envarsus XR

Intervention Description

0.07-0.14 mg/kg/day every morning orally

Primary Outcome Measure Information:

Title

1. Change in the percentage of donor specific antibodies

Description

Time Frame

Time of transplant and six months post-transplant

Title

Changes in the percentage of blood immunologic markers

Description

Time Frame

Time of transplant and six months post-transplant

Secondary Outcome Measure Information:

Title

Changes in creatinine clearance

Description

Baseline creatinine will be considered the creatinine plasma levels several days after transplantation once the kidney function is stabilized.

Time Frame

Time of transplant and six months post-transplant

Other Pre-specified Outcome Measures:

Title

Changes in GFR

Description

We will use the MDRD GFR equation to estimate glomerular filtration rate based on baseline creatinine and patient characteristics (age, gender and race)

Time Frame

30 Days post transplant and months 3 and 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Deepa Valvi, DrPH

Phone

8592579443

deepa.valvi@uky.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roberto Gedaly, MD

Organizational Affiliation

University of Kentucky

Official's Role

Principal Investigator

Facility Information:

Facility Name

Deepa Valvi

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Deepa Valvi, DrPH

Phone

859-257-9443

deepa.valvi@uky.edu

First Name & Middle Initial & Last Name & Degree

Roberto Gedaly, MD

First Name & Middle Initial & Last Name & Degree

TrisAnn Rendulic, PharmD

12. IPD Sharing Statement

Plan to Share IPD

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

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