COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01837043
Recruitment Status : Unknown
Verified January 2017 by Nair, Vinay, D.O..
Recruitment status was:  Recruiting
First Posted : April 22, 2013
Last Update Posted : January 30, 2017
Icahn School of Medicine at Mount Sinai
Bristol-Myers Squibb
Information provided by (Responsible Party):
Nair, Vinay, D.O.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Delayed Graft Function Kidney Transplant Drug: Belatacept Drug: Calcineurin Inhibitor Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Early Conversion From Calcineurin Inhibitors (CNI) to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
Study Start Date : June 2013
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Belatacept

Arm Intervention/treatment
Experimental: Belatacept
Subjects will be converted from standard of care CNI therapy to Belatacept 10 mg/kg IV on post renal transplant Day 7 (+/- 3 days). As suggested in the package insert for de novo dosing, further dosing of belatacept will be given as 10 mg/kg IV at weeks 2, 4, 8 and 12 then 5 mg/kg at week 16 and then every 4 weeks (+/- 5 days) through week 52. CNI will be stopped during the first belatacept infusion.
Drug: Belatacept
Other Name: Nulojix

Active Comparator: Calcineurin Inhibitor
Patients randomized to this arm will remain on the current CNI as prescribed by post-transplant standard of care therapy.
Drug: Calcineurin Inhibitor
Other Name: Prograf, Tacrolimus, Cyclosporine

Primary Outcome Measures :
  1. cGFR [ Time Frame: 12 months ]
    Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.

Secondary Outcome Measures :
  1. Renal Histology [ Time Frame: 12 months ]
    Chronic Allograft Damage Index (CADI) and Interstitial Fibrosis/Tubular Atrophy (IFTA) renal pathology scores will be assessed by a local pathologist. CADI and IF/TA will be recorded at baseline (reperfusion biopsy) and at the 1 year protocol biopsy. The average progression of CADI and IF/TA will be compared in both groups and the average absolute CADI and IF/TA scores will be compared in both groups at 1 year post transplant.

  2. Biomarker profile [ Time Frame: 12 months ]
    The results of urine biomarkers (clusterin) will be correlated with the development of the primary and secondary endpoints in both groups. In this manner the investigators will be able to understand which genes/proteins are primarily altered by injury and assess how belatacept affects this process.

  3. Duration of Delayed (or slow) Graft Function [ Time Frame: 12 months ]
    The average duration of DGF/SGF will be compared in both belatacept and CNI groups

  4. Incidence of Acute Rejection [ Time Frame: 12 months ]
    Acute rejection by month 12 will be assessed by a local pathologist using the Banff 97 working classification of kidney transplant pathology. All biopsies will be interpreted locally for purposes of the study.

  5. New Onset Diabetes [ Time Frame: 12 months ]
    Subjects will be evaluated for post-transplant diabetes at visits after week 4.

  6. Blood Pressure Control [ Time Frame: 12 months ]
    Subjects are to be evaluated at each clinic visit to assess the need for adjustment of antihypertensive medication in order to achieve a BP of < 130/80 mmHg. Average systolic and diastolic blood pressure in both groups at Month 12, number of antihypertensive medications and change in intensity of hypertension treatment will be observed.

  7. Dyslipidemia [ Time Frame: 12 months ]
    Cholesterol levels in both groups, number of patients on dyslipidemic therapy at month 12 and change in intensity of dyslipidemia therapy will be observed

  8. Graft Survival [ Time Frame: 12 Months ]
    Graft survival will be observed in both groups and compared at 12 months post-transplant

  9. Patient survival [ Time Frame: 12 months ]
    Patient survival will be observed in both groups and compared at 12 months post-transplant

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01837043

Layout table for location contacts
Contact: Vinay Nair, D.O. 212-659-8086
Contact: Brandy M Haydel, CCRC 212-241-0255

Layout table for location information
United States, New York
Mount Sinai School of Medicine Recanati/Miller Transplantation Institute Recruiting
New York, New York, United States, 10029
Contact: Vinay Nair, D.O.    212-659-8086   
Contact: Brandy Haydel, CCRC    212-241-0255   
Principal Investigator: Vinay Nair, D.O.         
Sub-Investigator: Sander Florman, MD         
Sub-Investigator: Peter Heeger, MD         
Sub-Investigator: Barbara Murphy, MD         
Sponsors and Collaborators
Nair, Vinay, D.O.
Icahn School of Medicine at Mount Sinai
Bristol-Myers Squibb
Layout table for investigator information
Principal Investigator: Vinay Nair, D.O. Icahn School of Medicine at Mount Sinai

Layout table for additonal information
Responsible Party: Nair, Vinay, D.O. Identifier: NCT01837043    
Other Study ID Numbers: IM103-057
13-00174 ( Other Identifier: Mount Sinai PPHS )
First Posted: April 22, 2013    Key Record Dates
Last Update Posted: January 30, 2017
Last Verified: January 2017
Keywords provided by Nair, Vinay, D.O.:
Delayed Graft Function
Renal Transplantation
Kidney Transplant
Additional relevant MeSH terms:
Layout table for MeSH terms
Delayed Graft Function
Pathologic Processes
Calcineurin Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents