Simplified IMmunosuppressive Protocol Utilizing Low Dose EnvarsusXR

NCT04773392 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: HS-18-00513
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the combination of once-daily tacrolimus extended-release (EnvarsusXR) and Azathioprine is non inferior with respect to the composite outcome of acute rejection, graft and patient survival as compared to a combination of twice-daily immediate release tacrolimus and mycophenolate mofetil/mycophenolic acid.

Conditions

Kidney Transplantation; Kidney Transplant Rejection

Keywords

tacrolimus; envarsus XR; kidney transplant; rejection; immunosuppressive agents; renal transplant

Outcome Measures

Primary Outcomes (3)

• To compare the composite incidence of biopsy proven acute rejection, graft survival and patient survival

  Biopsies will be performed for unexplained rise in serum creatinine or proteinuria and the development of donor specific antibodies. Biopsies will be assessed by a pathologist using standard Banff classification of renal allograft pathology. Graft loss will be defined as return to chronic dialysis or graft removal.

  3 months

• To compare the composite incidence of biopsy proven acute rejection, graft survival and patient survival

  Biopsies will be performed for unexplained rise in serum creatinine or proteinuria and the development of donor specific antibodies. Biopsies will be assessed by a pathologist using standard Banff classification of renal allograft pathology. Graft loss will be defined as return to chronic dialysis or graft removal.

  6 months

• To compare the composite incidence of biopsy proven acute rejection, graft survival and patient survival

  Biopsies will be performed for unexplained rise in serum creatinine or proteinuria and the development of donor specific antibodies. Biopsies will be assessed by a pathologist using standard Banff classification of renal allograft pathology. Graft loss will be defined as return to chronic dialysis or graft removal.

  12 months

Secondary Outcomes (15)

• Renal allograft function

  Every month, for a duration of 12 months

• Proteinuria

  Every month, for a duration of 12 months

• Donor-specific antibodies (DSA)

  3, 6, and 12 months

• Cytomegalovirus (CMV)

  3, 6, and 12 months

• Liver Function

  3, 6, and 12 months

Study Arms (2)

Twice-daily Regimen

ACTIVE COMPARATOR

Twice-daily regimen of immediate release tacrolimus, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) plus daily methylprednisolone or prednisone.

Drug: Twice-daily Tacrolimus; Drug: Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG); Drug: Methylprednisolone, prednisone; Drug: Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA)

Once-daily Regimen

ACTIVE COMPARATOR

Once-daily regimen of Envarsus, azathioprine plus methylprednisolone or prednisone.

Drug: Once-daily envarsus XR; Drug: Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG); Drug: Methylprednisolone, prednisone; Drug: Azathioprine

Interventions

Twice-daily Tacrolimus DRUG

Within 48 hours of transplantation, immediate release tacrolimus (IRT) (0.1 mg/kg /day) will be administered twice a day.

Also known as: immediate release tacrolimus

Twice-daily Regimen

Once-daily envarsus XR DRUG

Within 48 hours of transplantation, Envarsus XR (0.13mg/kg/day) will be administered once a day.

Also known as: extended releated tacrolimus

Once-daily Regimen

Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG) DRUG

Induction immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG) per protocol. The dose of Basiliximab will be a standard of two 20 mg doses and total rATG will not exceed 6 mg/kg.

Also known as: Simulect, ATG

Once-daily Regimen; Twice-daily Regimen

Methylprednisolone, prednisone DRUG

Methylprednisolone intraoperatively (500mg) and immediately post transplantation (200mg on post operative day (POD) #1, 150mg on POD#2, 100mg on POD#3) then oral prednisone (50mg on POD #4, 20mg on POD #5). Oral prednisone will be tapered down to a minimal dose of 5mg within 6 weeks post transplantation.

Also known as: Steroids

Once-daily Regimen; Twice-daily Regimen

Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA) DRUG

Mycophenolate mofetil (MMF) (up to 1000mg) or Mycophenolic acid (MPA) (up to 720mg) will be administered twice a day.

Also known as: Twice a day anti-metabolite

Twice-daily Regimen

Azathioprine DRUG

Azathioprine (1-3 mg/kg) will be administered once a day.

Also known as: Once a day anti-metabolite

Once-daily Regimen

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• De- Novo Kidney transplant patients between 18 and 85 years old
• Cold ischemia time (CIT) \< 24 hours for 3-6 HLA mismatches between donor and recipient and CIT \>24 hours for HLA mismatch of less than 3 between donor and recipient
• Most recent pre-transplant cPRA (calculated panel reactive antibody) ≤ 20%

You may not qualify if:

• Repeat kidney transplant recipients
• cPRA \>20%
• rATG (rabbit anti-thymocyte globulin) induction \>6mg/kg at time of induction
• Crossmatches deemed positive by accepting physician
• Presence of pre-formed anti-HLA (anti-Human Leukocyte Antigen) DSA (Donor-Specific Antibody) as defined by MFI (mean fluorescence intensity) approaching 3000 using flow cytometry/Luminex-based, specific anti-HLA antibody testing.
• Receipt of desensitization protocols
• History of skin cancer
• Recipient of multi-organ or dual kidney transplants
• For any condition, in which the investigator's opinion makes the subject unsuitable for study

Sponsors & Collaborators

• University of Southern California: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

Location

Related Publications (4)

• Park SI, Felipe CR, Pinheiro-Machado PG, Garcia R, Fernandes FB, Casarini DE, Tedesco-Silva H Jr, Medina-Pestana JO. Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus. Fundam Clin Pharmacol. 2009 Feb;23(1):137-45. doi: 10.1111/j.1472-8206.2008.00644.x.

  PMID: 19267777 BACKGROUND

• Dalal P, Shah G, Chhabra D, Gallon L. Role of tacrolimus combination therapy with mycophenolate mofetil in the prevention of organ rejection in kidney transplant patients. Int J Nephrol Renovasc Dis. 2010;3:107-15. doi: 10.2147/ijnrd.s7044. Epub 2010 Aug 4.

  PMID: 21694936 BACKGROUND

• Kulich KR, Madisch A, Pacini F, Pique JM, Regula J, Van Rensburg CJ, Ujszaszy L, Carlsson J, Halling K, Wiklund IK. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008 Jan 31;6:12. doi: 10.1186/1477-7525-6-12.

  PMID: 18237386 BACKGROUND

• Troster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation. Parkinsonism Relat Disord. 2005 Sep;11(6):367-73. doi: 10.1016/j.parkreldis.2005.05.009.

  PMID: 16103000 BACKGROUND

Related Links

• Prescribing information

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Basiliximab; Methylprednisolone; Prednisone; Steroids; Mycophenolic Acid; Azathioprine

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Santhi Voora, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is an open-label, randomized, prospective clinical trial. Patients will be screened prior to surgery and randomized 1:1 to each arm.

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: February 26, 2021
• Study Start: November 23, 2021
• Primary Completion: February 23, 2024
• Study Completion: February 23, 2024
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)