Kidney Transplantation
Conditions
Brief summary
The primary objective of this study is to demonstrate that administration of belatacept in maintenance kidney transplant recipients may cause a reduction in Donor Specific HLA Antibody (DSA).
Detailed description
The aim of this study is to evaluate patients converted to belatacept in combination with Mycophenolate Mofetil (MMF) with corticosteroids with respect to their DSA titer. Patients in this study will be converted from their calcineurin inhibitor (CNI) to belatacept from baseline in an attempt to down-modulate antibody production by B-cells. Dosing will be calculated per prescribing information for dosing maintenance phase (5mg per kg every 28 days.
Interventions
DRUGBelatacept
Patients will be converted from their MMF to Belatacept
Sponsors
East Carolina University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Recipients of cadaveric, living related or living unrelated kidney transplant with positive DSA titer (two positive tests) and enrolled within 6 months of DSA detection. * Patients with stable renal function. Stable renal function is defined as one serum creatinine (SCr) value that is +/- 10% of the baseline SCr within 3 months of enrollment (eGFR \>/= 35 and \</= 75 mL/min/1.73m\^2). * Patients who are EBV seropositive * Males and females, 18-75 years of age; * Patients currently receiving mycophenolic acid (MPA) (CellCept daily or myfortic daily), cyclosporine or tacrolimus with corticosteroids as part of their immunosuppressive regimen * Patients willing to be converted to belatacept from cyclosporine or tacrolimus. * Females of childbearing potential must have a negative pregnancy test prior to enrollment. The test should be performed at baseline visit. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication; * Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.
Exclusion criteria
* Multi-solid or cellular organ transplants (e.g. combined with pancreas, liver, islet, bone marrow), either concurrent or previous (with exception that a second kidney transplant is allowed); * Evidence of graft rejection or treatment of acute rejection within 14 days prior to Baseline visit; * Patients who have received any investigational drug within 4 weeks prior to study entry; * Patients with HLA identical * Patients who are Epstein-Barr virus (EBV) seronegative * Presence of clinically significant infection requiring continued therapy, chronic infection (e.g. HIV, Hep B and Hep C), malignancy (within last 5 years, except excised squamous or basal cell carcinoma of the skin), lymphoma or renal toxicity that would interfere with the appropriate conduct of the study; * Evidence of severe liver disease (incl. abnormal liver profile i.e. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) or total bilirubin \>/= 3 times ULN) or severe diarrhea or active peptic ulcer disease that would interfere with the appropriate conduct of the study; * Abnormal physical or laboratory findings of clinical significance within 2 weeks of inclusion which would interfere with the objectives of the study; * Patients with symptoms of significant somatic or mental illness or evidence of drug and/or alcohol abuse; * Patients receiving \> 10 mg/day prednisone dose; * History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures to belatacept; * Patients not making DSA antibodies; * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (local); females of childbearing potential who are unwilling to use effective study-approved contraceptives and who are planning to become pregnant; Sexually active fertile men must use effective birth control if their partners are women of child bearing potential; * Any other medical condition that, in the opinion of the site investigator based on recall or chart review would interfere with completing the study, including but not limited to visual problems or cognitive impairment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Donor Specific Antibodies (DSA) | one year | DSA levels will be measured using microbeads coated with Class I or Class II human leukocyte antigens (HLA) and read using a Luminex flow cytometer. Participants will be converted from their current Mycophenolate Mofetil (MMF) to once a month infusions of Belatacept. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety | one year | Incidence of infections |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Chronic Kidney Rejection | One year | Incidence of chronic kidney rejection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belatacept All patients enrolled will be converted to Belatacept from prograf. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Belatacept |
|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 5.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Change of Donor Specific Antibodies (DSA)
DSA levels will be measured using microbeads coated with Class I or Class II human leukocyte antigens (HLA) and read using a Luminex flow cytometer. Participants will be converted from their current Mycophenolate Mofetil (MMF) to once a month infusions of Belatacept.
Time frame: one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belatacept | Change of Donor Specific Antibodies (DSA) | 35.7 percent change in DSAs | Standard Deviation 45.8 |
Secondary
Safety
Incidence of infections
Time frame: one year
Population: Number of participants with infections
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belatacept | Safety | 2 Participant |
Other Pre-specified
Number of Participants With Chronic Kidney Rejection
Incidence of chronic kidney rejection
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belatacept | Number of Participants With Chronic Kidney Rejection | 0 participants |