Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation

Kidney transplantation is a treatment option for people with kidney disease. However, there
is still much to learn about how to best care for the transplanted kidney and keep it
functioning for a long time. Transplant recipients take immunosuppression (anti-rejection)
drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent
the immune system from attacking the transplanted kidney. All anti-rejection medications
have unwanted side effects. The purpose of this study is to evaluate the safety of slowly
removing tacrolimus, a CNI.

POST STUDY TERMINATION NOTE: Although the investigators were unable to assess the primary
study end point due to early study termination,this trial supports the conclusion that risks
associated with acute rejection and donor-specific antibodies outweigh any potential
benefits of tacrolimus withdrawal, even in this highly selected, low-risk cohort of living
donor recipients treated with antithymocyte globulin induction.

INCLUSION CRITERIA -

Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible
for enrollment as study subjects:

- Subject must be able to understand and provide written informed consent;

- Primary living-donor (related or unrelated) kidney transplant recipients;

- Peak flow-based PRAs for class I and class II <30%(performed by local center);

- Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and
class II <30% (performed by local center);

- No donor specific antibody by flow solid phase method on the peak PRA serum (if serum
available), or on the current PRA serum (within 8 weeks prior to transplantation)
performed by central core laboratory. If the sera for the peak PRA is not available,
then only the current PRA serum will be tested;

- Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);

- Female subjects of childbearing potential must have a negative pregnancy test (urine
or serum) upon study entry;

- Female and male subjects with reproductive potential must agree to use FDA approved
methods of birth control while participating in the study.

Inclusion Criteria for Randomization:

Participants who meet all of the following criteria are eligible for randomization:

- No history of acute rejection episodes;

- The pre-randomization protocol biopsy should confirm no rejection, including
borderline rejection (based on the central pathology read);

- No donor specific antibody as detected by flow solid phase method (performed by the
central core laboratory).

EXCLUSION CRITERIA -

Initial Enrollment/Screening:

Participants who meet any of these criteria are not eligible for enrollment as study
subjects:

- Recipient of multiple organ transplants;

- Prior history of organ transplantation;

- Deceased-donor source;

- Any condition that would preclude protocol biopsies;

- HLA identical recipients;

- Currently breast-feeding or plans to become pregnant during the timeframe of the
study follow up period;

- Any condition that, in the opinion of the investigator, would interfere with the
subject's ability to comply with study requirements;

- Inability or unwillingness to comply with study protocol;

- Use of investigational drugs within 4 weeks of study entry and for the duration of
the study;

- Recent recipient of any licensed or investigational live attenuated vaccine(s) within
two months of prior to study entry.

Exclusion Criteria for Randomization:

Participants who meet any of these criteria are not eligible for randomization:

- Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction
therapy;

- Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;

- Any condition that would preclude protocol biopsies;

- Currently breast-feeding or plans to become pregnant during the timeframe of the
study follow up period;

- Any condition that, in the opinion of the investigator, would interfere with the
subject's ability to comply with study requirements;

- Inability or unwillingness of a subject to give written informed consent or comply
with study protocol;

- Use of investigational drugs within 4 weeks of study entry and for the duration of
the study;

- Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or
equivalent.