Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 2

Conditions: Kidney Transplantation; Primary Renal Allograft Candidate

Treatments: Biological: Anti-thymocyte Globulin (Rabbit); Biological: belatacept; Biological: basiliximab; Drug: mycophenolate mofetil; Drug: methylprednisolone; Drug: tacrolimus

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01856257

DAIT CTOT-16

Details and patient eligibility

About

The primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of improving long-term graft function without increasing the risks of immunologic graft injury by avoiding both calcineurin inhibitors (CNIs) and corticosteroids.

Full description

Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. 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 receive a kidney transplant must take these anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work.

The purpose of this study is to determine if NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted kidney.

Enrollment: 71 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 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;
• Participants with reproductive potential must agree to use an appropriate method(s) of birth control as outlined in the CellCept® , Myfortic® or generic package labeling during participation in the study and for 4 months following completion of the study;
• No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
• Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current sera, as determined by each participating study center;
• A documented negative tuberculosis (TB) test within the 6 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;

• Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;

• Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (HIV);

• Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;

• Individuals undergoing transplant using organs from extended criteria donor (ECD) or donation after cardiac death (DCD) donors;

• Histocompatibility antigen (HLA) identical living donors;

• Individuals at significant risk of early recurrence of the primary renal disease including focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (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;

• Known history of thrombotic events or risk factors, including any of the following:

  • Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin-induced thrombocytopenia,
  • A family history of a heritable thrombotic condition,
  • Recurrent deep vein thrombosis (DVT) or pulmonary emboli (PE),
  • Unexplained stillborn infant or recurrent spontaneous abortion or other congenital or acquired thrombotic disorder.

At the discretion of the investigator, a history of thrombosis of a dialysis access graft, fistula, or indwelling catheter/device may not be considered an exclusion criterion.

• 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;
• Blood type A2 and A2B donors into blood type B recipients.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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71 participants in 3 patient groups

Thymoglobulin®+tacrolimus+MMF

Active Comparator group

Description:

Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)

Treatment:

Drug: tacrolimus

Drug: methylprednisolone

Drug: mycophenolate mofetil

Biological: Anti-thymocyte Globulin (Rabbit)

Thymoglobulin®+belatacept+MMF

Experimental group

Description:

Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)

Treatment:

Drug: methylprednisolone

Drug: mycophenolate mofetil

Biological: belatacept

Biological: Anti-thymocyte Globulin (Rabbit)

Basiliximab+20 weeks of tacrolimus+MMF + belatacept

Experimental group

Description:

Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent. Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.

Treatment:

Drug: tacrolimus

Drug: methylprednisolone

Drug: mycophenolate mofetil

Biological: basiliximab

Biological: belatacept