Veloxis de Novo Kidney Transplant ECSWD

A 12-Month, Open Label Study of Extended Release Tacrolimus (Envarsus XR®, LCPT) With Mycophenolate, Rabbit Antithymocyte Globulin (rATG) and Early Steroid Withdrawal in de Novo Kidney Transplant Recipients

This study is designed to evaluate the safety and efficacy of LCPT in combination with rATG, mycophenolate and early corticosteroid withdrawal (CSWD) in de novo kidney transplant recipients.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplantation; Immunosuppression
• Intervention / Treatment: Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]; Drug: Mycophenolate Mofetil; Drug: Mycophenolic Acid Oral Product; Drug: Methylprednisolone; Drug: Prednisone; Drug: Rabbit Anti-Human T-Lymphocyte Globulin Injectable Solution [Thymoglobulin]; Drug: Tacrolimus

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Simon Tremblay, PharmD, PhD; Phone Number: 513-558-9967; Email: tremblsn@ucmail.uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Contact: Simon Tremblay, PharmD, PhD; Phone Number: 513-558-9967; Email: simon.tremblay@uc.edu
      • Sub-Investigator: Ervin S Woodle, MD
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
      • Contact: Simon Tremblay, PharmD, PhD; Phone Number: 513-558-9967; Email: simon.tremblay@uc.edu
      • Sub-Investigator: Ervin S Woodle, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients ≥ 18 years of age.
2. Patient who is receiving a renal transplant from a living or heart-beating deceased donor.
3. Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.
4. The patient has given written informed consent to participate in the study

Exclusion Criteria:

1. Patient has previously received an organ transplant other than a kidney.
2. Patient is receiving an HLA identical living donor transplant.
3. Patient who is a recipient of a multiple organ transplant.
4. Patient has a most recent cytotoxic PRA of >25% or calculated PRA >50% where multiple moderate level HLA antibodies exist and in the opinion of the PI represents substantial HLA sensitization.
5. Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies.
6. Patient with a donor specific antibody (DSA) as deemed by the PI to be associated with significant risk of rejection.
7. Patient has received an ABO incompatible donor kidney.

8. The deceased donor and/or deceased donor kidney meet any of the following extended criteria for organ donation (ECD):

   1. Donor age ≥ 60 years OR
   2. Donor age 50-59 years and 1 of the following:

   i. Cerebrovascular accident (CVA) + hypertension + SCr > 1.5 mg/dL OR ii. CVA + hypertension OR iii. CVA + SCr > 1.5 mg/dL OR iv. Hypertension + SCr > 1.5 mg/dL OR c. CIT ≥ 24 hours, donor age > 10 years OR d. Donation after cardiac death (DCD)

9. Recipients will be receiving a dual or en bloc kidney transplant.
10. Donor anticipated cold ischemia is >30hours.
11. Recipient that is seropositive for hepatitis C virus (HCV) with detectable Hepatitis C viral load are excluded. HCV seropositive patients with a negative HCV viral load testing may be included.
12. Recipients with a positive hepatitis B viral load or positive hepatitis B surface antigen testing within 1 year of consent.
13. Hepatitis B surface antibody negative recipients receiving a kidney from a donor seropositive for hepatitis B core antibody or hepatitis B nucleic acid.
14. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).
15. Recipient who is seronegative for Epstein Barr Virus (EBV)
16. Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
17. Patients with thrombocytopenia (PLT <75,000/mm3), and/or leukopenia (WBC < 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.
18. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.
19. Patient who has undergone desensitization therapy within 6 months prior to transplant.
20. Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil/mycophenolic acid, rabbit anti-thymocyte globulin, or glucocorticoids.
21. Patient is receiving chronic steroid therapy at the time of transplant.
22. Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years, unless they have an expected disease free survival of >95%.
23. Patient is pregnant, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.
24. Women of childbearing potential must use reliable contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
25. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.
26. Inability to cooperate or communicate with the investigator.
27. Renal allograft has been reperfused for more than 48 hours at the time of enrollment
28. Patient unable to receive intact LCPT formulation

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospective Arm; De novo kidney transplant recipients receiving: rabbit antithymocyte globulin induction (1.5mg/kg, dosage range 4-6mg/kg total dose over 5-10 days) 5-day steroid withdrawal (methylprednisolone 500mg IV on day 1 (day of transplant), 250mg IV on day 2, 125mg IV on day 3, prednisone 80mg PO on day 4, 60mg PO on day 5 and then no more steroids Once-daily tacrolimus XR 0.8mg/kg/day started when or when serum creatinine is <4mg/dL or by 48 hours of transplant to target 24-hr trough levels of 8-12ng/mL up to day 30 followed by 24-hour trough targets of 5-10ng/mL Mycophenolate mofetil (1000 mg PO BID) or mycophenolic acid (720mg PO BID) twice daily started prior to surgery	Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]; Tacrolimus Extended Release Oral Tablet [Envarsus]; Other Names: Envarsus XR; Drug: Mycophenolate Mofetil; Mycophenolate mofetil capsules or tablets; Other Names: Cellcept; MMF; Drug: Mycophenolic Acid Oral Product; mycophenolic acid tablets; Other Names: Myfortic; MPA; Drug: Methylprednisolone; Methylprednisolone taper; Drug: Prednisone; Prednisone taper; Other Names: Deltasone; Drug: Rabbit Anti-Human T-Lymphocyte Globulin Injectable Solution [Thymoglobulin]; Rabbit Anti-Human T-Lymphocyte Globulin; Other Names: Thymoglobulin; rATG
Active Comparator: Comparator arm; Historical control arm consisting of the following De novo kidney transplant recipients receiving: rabbit antithymocyte globulin induction (1.5mg/kg, dosage range 4-6mg/kg total dose over 5-10 days) 5-day steroid withdrawal (methylprednisolone 500mg IV on day 1 (day of transplant), 250mg IV on day 2, 125mg IV on day 3, prednisone 80mg PO on day 4, 60mg PO on day 5 and then no more steroids Twice-daily tacrolimus 0.1mg/kg/day started when or when serum creatinine is <4mg/dL or by 48 hours of transplant to target 12-hr trough levels of 8-12ng/mL up to day 30 followed by 12-hour trough targets of 5-10ng/mL Mycophenolate mofetil (1000 mg PO BID) or mycophenolic acid (720mg PO BID) twice daily started prior to surgery	Drug: Mycophenolate Mofetil; Mycophenolate mofetil capsules or tablets; Other Names: Cellcept; MMF; Drug: Mycophenolic Acid Oral Product; mycophenolic acid tablets; Other Names: Myfortic; MPA; Drug: Methylprednisolone; Methylprednisolone taper; Drug: Prednisone; Prednisone taper; Other Names: Deltasone; Drug: Rabbit Anti-Human T-Lymphocyte Globulin Injectable Solution [Thymoglobulin]; Rabbit Anti-Human T-Lymphocyte Globulin; Other Names: Thymoglobulin; rATG; Drug: Tacrolimus; Twice daily tacrolimus; Other Names: Prograf; FK506

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with the combination oral outcome of Biopsy-proven acute rejection, patient death and graft loss	Biopsy-proven acute rejection, patient death and graft loss	12 months

Collaborators and Investigators

• Sponsor: Simon Tremblay, PharmD, PhD
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Simon Tremblay, PharmD, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2019
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: kidney transplantation; tacrolimus; once daily; extended release; steroid withdrawal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Methylprednisolone; Prednisone; Tacrolimus; Mycophenolic Acid; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: 2018-7742

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