Belatacept in Kidney Transplantation of Moderately Sensitized Patients

This exploratory single-center, open-label safety and efficacy study will enroll 20 adult
kidney transplants candidates, moderately sensitized against their deceased donor and at-risk
for delayed graft function (DGF), to receive Belatacept (days 0,5, weeks 2,4,8 and 12 (10
mg/kg), and every 4 weeks thereafter (5 mg/kg)), plasma exchange (once before and twice after
transplant) and Intravenous Immunoglobulin (IVIG) (100 mg/kg after each plasma exchange),
along with Thymoglobulin (ATG) induction and Dexamethasone tapered dosing starting on the day
of transplant at 100mg IV, tapered through Day 4, followed by prednisone at 30 mg on Day 5
with tapered dosing to prednisone 10 mg/d by one month, with a total observation period of 1
year. Patients will be tapered off tacrolimus by week 8 and will remain on mycophenolic acid
and prednisone for the total length of the study. Subjects will be followed until 1 year post
transplant.

Inclusion Criteria:

- Male or female subjects 18-70 years of age

- Patient who is receiving an expanded criteria donor (ECD) or deceased cardiac donor
(DCD) kidney

- Have immunodominant donor specific antibodies (DSA) 1,000 - 4,000 mean fluorescent
intensity (MFI) by single bead Luminex bioassay

- Subjects must be capable of understanding the investigational nature and risks of the
study and must sign a statement of informed consent

- Female patients of child bearing potential must have a negative urine or serum
pregnancy test within the past 48 hours prior to study inclusion and be willing to use
contraceptives for the duration of the study and for 8 weeks after the last dose of
study drug Women of Child-Bearing Potential (WOCBP) includes

- Women who have experienced menarche and who have not undergone successful surgical
sterilization or who are not post-menopausal

- Women using oral contraceptives, other hormonal contraceptives, or mechanical products
such as intrauterine devices or barrier methods

- Women who are practicing abstinence

- Women who have a partner who is sterile (eg, due to vasectomy).

- Women must not be breast-feeding

- Male subjects must agree to use an acceptable method for contraception for the
duration of the study

- Patient must have known positive Epstein-Barr virus (EBV) serostatus

Exclusion Criteria:

- Patient has previously received an organ transplant other than a kidney.

- Patient is receiving an human leukocyte antigen (HLA) identical living donor
transplant

- Patient who is a recipient of a multiple organ transplant

- Patient with a positive T or B cell crossmatch

- Patient with a donor specific antibody (DSA) as deemed by the local PI to be
associated with significant risk of rejection

- Patient has received an ABO incompatible donor kidney

- Recipients will be receiving a dual or en bloc kidney transplant

- Donor anticipated cold ischemia is > 30hours

- Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus
(HBV) except for hepatitis B surface antibody positive. HCV seropositive patients with
a negative HCV viral load testing may be included.

- Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)

- Seronegative or unknown EBV serostatus

- Patient has uncontrolled concomitant infection or any other unstable medical condition
that could interfere with the study objectives

- Patients with tuberculosis who have not been treated for latent infection.

- Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to
BK virus infection

- Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to
BK virus infection

- Patients with thrombocytopenia (PLT <75,000/mm3), and/or leucopoenia (WBC <
2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.

- Patient is taking or has been taking an investigational drug in the 30 days prior to
transplant

- Patient who has undergone desensitization therapy within 6 months prior to transplant

- Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil,
alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids

- Patient is receiving chronic steroid therapy at the time of transplant

- Patients with a history of cancer (other than non-melanoma skin cell cancers cured by
local resection) within the last 5 years

- Patients with > Grade 2 peripheral neuropathy within 14 days before enrollment

- Myocardial infarction within 6 months prior to enrollment or New York Heart
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiography evidence of acute
ischemia or active conduction system abnormalities.

- Female subject is pregnant or breast-feeding

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study. Subjects who are compulsorily detained for treatment of either a
psychiatric or physical illness

- Prisoners or subjects who are involuntarily incarcerated