Mycophenolic Acid Monotherapy in Recipients of HLA-identical Living-Related Transplantation

This randomized trial will enroll adult recipients of HLA-identical living kidney transplants who are at least 1 year post-transplant. All subjects will be taking Prograf (tacrolimus) or cyclosporine and mycophenolic acid (CellCept or Myfortic) and then be randomized (1:2) to either continue calcineurin inhibitors or to taper off of calcineurin inhibitors. The hypothesis is that mycophenolic acid monotherapy permits long-term rejection-free renal allograft function in the absence of long-term calcineurin inhibitors in this fully matched renal transplant cohort.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Mycophenolic Acid; Drug: Standard of Care: CNI and MPA

Detailed Description

The objective of the study is to safely move HLA-identical renal transplant recipients from 2 immunosuppressive drugs (calcineurin inhibitor and mycophenolic acid) to mycophenolic acid monotherapy. Safety will be assessed by monitoring renal function in subjects in the withdrawal group compared to those who remain on the standard 2-drug immunosuppression protocol. Results of immunological monitors such as DTH regulation in response to donor minor antigens and development of anti-donor antibodies will be correlated with successful withdrawal.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female subjects 18-75 years of age.
• Subjects who are recipients of HLA-identical living donor renal allografts from a sibling and are at least 1 year post transplant, their donors and mothers.
• Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

• GFR <40ml/min;
• diagnosis of SLE,
• Subjects with proteinuria (defined as a protein:creatinine ratio of >1 or an amount less than this deemed significant on an individual subject basis by the principal investigator),,
• multi-organ transplant;
• known hypersensitivity to, Prograf, Neoral, CellCept or Myfortic;
• history of documented post transplant non-compliance with medications, transplant clinic or laboratory follow-up;
• therapy with an investigational immunosuppressive drug within 6 weeks of study entry;
• history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study;
• patients on less than 500 mg PO BID of CellCept or 360 mg PO BID of Myfortic at the time of potential randomization,
• history of humoral rejection post transplant,
• maintenance or for cause treatment with steroids (prednisone) within 3 months of enrollment.

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
Experimental: MPA monotherapy; Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy	Drug: Mycophenolic Acid; Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months; Other Names: cellcept, myfortic
Active Comparator: Control: MPA and CNI; Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus)	Drug: Standard of Care: CNI and MPA; Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Kidney Allograft Rejection and Graft Loss	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Function Measured by Serum Creatinine and eGFR		36 months
Number of Incidences of Infection and Malignancy	Number of incidences of infection and malignancy will be reported.	36 months
Patient Survival	patient survival	36 months
Trans-vivo Delayed Type Hypersensitivity (DTH) Assay	Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal.	36 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: William Burlingham, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: January 19, 2010
• First Submitted That Met QC Criteria: January 20, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: June 25, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: living donor; mycophenolate
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: H-2005-0357; 2012-0343 (Other Identifier: HS-IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No