Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology, Other |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | June 2013 |
| End Date: | June 2017 |
| Contact: | Vinay Nair, D.O. |
| Email: | Vinay.Nair@mountsinai.org |
| Phone: | 212-659-8086 |
A Randomized Trial of Early Conversion From Calcineurin Inhibitors (CNI) to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
The purpose of this study is to evaluate the safety and efficacy of conversion from a
calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix®
(belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function
(SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at
the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they
have developed SGF or DGF they will be randomized to convert to Belatacept or continue on
their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control
subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal
biopsy at Month 12 post transplant.
Research Hypotheses:
Primary Hypotheses:
- Kidneys with slow or delayed graft function are more susceptible to acute and long-term
CNI toxicity
- Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a
more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have
improved 1 year calculated GFR.
Key Secondary Hypotheses:
- Renal Histology: Belatacept converted patients will have a lower chronic allograft
damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA)
score as calculated by Banff criteria at 1 year post- transplant
- Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections
can 1) directly assess CNI induced kidney injury and 2) improve the prediction of
patients that benefit in early belatacept conversion.
calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix®
(belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function
(SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at
the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they
have developed SGF or DGF they will be randomized to convert to Belatacept or continue on
their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control
subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal
biopsy at Month 12 post transplant.
Research Hypotheses:
Primary Hypotheses:
- Kidneys with slow or delayed graft function are more susceptible to acute and long-term
CNI toxicity
- Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a
more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have
improved 1 year calculated GFR.
Key Secondary Hypotheses:
- Renal Histology: Belatacept converted patients will have a lower chronic allograft
damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA)
score as calculated by Banff criteria at 1 year post- transplant
- Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections
can 1) directly assess CNI induced kidney injury and 2) improve the prediction of
patients that benefit in early belatacept conversion.
Inclusion Criteria:
- Before any study procedures are performed, subjects will have the details of the
study described to them, and they will be given a written informed consent document
to read. Then, if subjects consent to participate in the study, they will indicate
that consent by signing and dating the informed consent document in the presence of
study personnel.
- All patients (> 18 years) who have received a deceased donor transplant and are at
risk for SGF/DGF will be studied
- All gender and ethnicities will be considered in this study
- At risk for SGF/DGF is defined as:
- ECD (Extended Criteria Donor) donor kidney recipients
- ECD is defined as a donor over the age of 60 or age 50 to 60 with 2 of the
following risk factors:
- Terminal creatinine > 1.5 mg/dL
- History of Hypertension
- Death due to cerebrovascular accident
- Donations after cardiac death (DCD) kidney recipients
- Donor organs with an actual cold ischemia time (CIT) > 19 hours
- Recipients of donor organs with a terminal creatinine > 1.5 mg/dL
- Only patients who receive Thymoglobulin induction and CNI maintenance at time of
randomization will be considered for the study
- Men and women, 18 to 70 years of age
- Reproductive status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP
comprises women who have experienced menarche and who have not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral
oophorectomy) or who are not post-menopausal.
Post-menopause is defined as:
- Women who have had amenorrhea for >= 12 consecutive months (without another cause)
and who have a documented serum follicle-stimulating hormone (FSH)level > 35 mIU/mL
- Women who have irregular menstrual periods and a documented serum FSH level > 35
mIU/mL
- Women who are taking hormone replacement therapy
The following are WOCBP:
- Women using the following methods to prevent pregnancy: oral contraceptives, other
hormonal contraceptives (vaginal products, skin patches, or implanted or injectable
products), or mechanical products such as intrauterine devices or barrier methods
(diaphragm, condoms, spermicides).
- Women who are practicing abstinence
- Women who have a partner who is sterile (due to vasectomy)
- WOCBP must be using an acceptable method of contraception to avoid pregnancy
throughout the study and for up to 8 weeks after the last dose of study drug in such
a manner that the risk of pregnancy is minimized
- WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity
25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study
drug.
- Women must not be breast-feeding
- Sexually active fertile men must use effective birth control if their partners are
WOCBP
Exclusion Criteria:
- Seronegative or unknown EBV (Epstein Barr Virus) serostatus (due to the risk of
posttransplant lymphoproliferative disorder, PTLD) predominantly involving the
central nervous system
- 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
- Rejection episode before randomization
- Anatomic cause of SGF/DGF such as urinary leak, obstruction or thrombosis
- Patients with a prior or concurrent non-renal solid organ transplant
- Patients with living donor kidneys
- Patients with pediatric kidneys (age of less than 5 years)
- Dual kidney transplants (from the same donor)
- Immunologically high risk patients with a positive crossmatch pre- transplantation or
donor specific antibody (DSA) > 5000 MFI
- ABO Incompatible transplantation
- Patients with HIV
- Subjects with any active infection or other contraindication that would normally
exclude transplantation
- Patients with a history of malignancy in the last 5 years except non- melanoma skin
cancer
- Baseline white blood cell count less than 2,000
- Baseline hemoglobin less than 8 g/dL
- Patients with prior allergic reactions to belatacept
- Patients with prior allergic reactions to thymoglobulin
- Sex and Reproductive status - see WOCBP information in inclusion above
- Subjects currently receiving immunosuppressive agent(s) for other indications such as
an autoimmune disease or subjects with comorbidities that treatment with such agents
are likely during the trial.
- Subjects who have used any investigational drug within 30 days prior to the Day 1
visit
- Subjects previously treated with belatacept
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g. infectious disease) illness.
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