Optimization of NULOJIX® (Belatacept) Usage As A Means of Avoiding Calcineurin Inhibitor (CNI) and Steroids in Renal Transplantation

• Histological evidence of rejection and graft dysfunction [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Incidence of clinically suspected and biopsy proven acute rejection as defined by histologic evidence of rejection and graft dysfunction
• Measures of renal function and injury [ Time Frame: 52, 104, and 156 weeks ] [ Designated as safety issue: Yes ]
  Measures include eGFR < 60 mL/min/1.73 m2 by CKD-EPI; change in chronic kidney disease (CKD) stages from baseline; proportion of subjects with defined CKD stage 4 or 5; mean calculated eGFR; slope of eGFR by CKD-EPI over time based on serum creatinine; incidence of delayed graft function; increase of one or more grades of chronic allograft nephropathy (CAN)/interstitial fibrosis and tubular atrophy (IFTA) when comparing the implantation and subsequent protocol biopsies; incidence of CAN/IFTA grade I, II or III
• Assessment of the incidence and severity of rejection and anti-donor reactivity [ Time Frame: 52, 104, and 156 weeks ] [ Designated as safety issue: Yes ]
  Acute cellular rejection; severity of first and highest grade of acute cellular rejection; antibody mediated rejection; type of treatment of rejection; prevalence of de novo anti-donor HLA antibodies
• Measures of cardiovascular and metabolic parameters [ Time Frame: 2 - 156 weeks ] [ Designated as safety issue: Yes ]
  Include incidence of new onset diabetes after transplant or impaired fasting glucose; incidence of treated diabetes; HbA1c; standardized blood pressure measurement and use of anti-hypertensive medications; fasting lipid profile
• Incidence of graft rejection [ Time Frame: 156 weeks ] [ Designated as safety issue: Yes ]
• Incidence of death or graft loss [ Time Frame: 156 weeks ] [ Designated as safety issue: Yes ]
• Incidence of infections [ Time Frame: 156 weeks ] [ Designated as safety issue: Yes ]
• Immune reactivity and function assessed by research laboratory assays [ Time Frame: 156 weeks ] [ Designated as safety issue: No ]

Dialysis or kidney transplant are the two ways to treat kidney failure. Transplant recipients have to take anti-rejection medications to prevent their immune system (the body's natural defense system against illness) from rejecting their new kidney. Most patients who undergo a kidney transplant must take these anti-rejection medications for the rest of their lives. Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but don't damage the kidney. The purpose of this study is to find out if a new drug, NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the new kidney from damage. The researchers also want to learn more about the safety of this treatment and long term health of the transplanted kidney.

• Drug: Alemtuzumab induction
• Drug: MMF
• Drug: Basiliximab induction
• Drug: Short-term (3 months) Tacrolimus
  Short-term (3 months)
• Drug: Tacrolimus
  maintenance
• Drug: Belatacept
  maintenance

• Active Comparator: Tacrolimus maintenance
  Interventions:

  • Drug: Alemtuzumab induction
  • Drug: MMF
  • Drug: Tacrolimus
• Experimental: Belatacept maintenance
  Interventions:

  • Drug: Alemtuzumab induction
  • Drug: MMF
  • Drug: Belatacept
• Experimental: Basiliximab induction and Short-term Tacrolimus
  Short term = 3 months
  Interventions:

  • Drug: MMF
  • Drug: Basiliximab induction
  • Drug: Short-term (3 months) Tacrolimus
  • Drug: Belatacept

Inclusion Criteria:

• Male or Female, 18-65 years of age at the time of enrollment;
• Ability to understand and provide written informed consent;
• Candidate for primary renal allograft from either a living or deceased-donor;
• No known contraindications to study therapy using NULOJIX® (belatacept);
• Female participants of childbearing potential must have a negative pregnancy test upon study entry;
• Female and male participants with reproductive potential must agree to use FDA approved methods of birth control during participation in the study and for 4 months following completion of the study;
• Flow-based PRA within last 12 months (in absence of a sensitizing event) of < 30% as determined by each participating study center. If the subject experienced a sensitizing event after the PRA test date, then the PRA must be repeated and confirmed <30%;
• Negative crossmatch or a PRA of 0% on historic and admission sera as determined by each participating study center.
• A documented negative TB test within the 12 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.

Exclusion Criteria:

• Need for multi-organ transplant;
• Recipient of previous organ transplant;
• EBV sero-negative (or unknown) recipients;
• Active infection including hepatitis B, hepatitis C, or HIV;
• Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;
• Individuals undergoing transplant using organs from ECD or DCD donors;
• HLA identical living donors;
• Individuals at significant risk of early recurrence of the primary renal disease including FSGS and MPGN type 2 or any other disease that in the opinion of the investigator is at increased likelihood of recurrence and which may result in rapid decline in renal function;
• Individuals previously treated with NULOJIX® (belatacept);
• Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
• Use of investigational drugs within 4 weeks of enrollment;
• Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;
• Administration of live attenuated vaccine(s) within 8 weeks of enrollment.