Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 2

Conditions: Simultaneous Kidney and Pancreas Transplantation

Treatments: Biological: Anti-thymocyte Globulin (Rabbit); Drug: Mycophenolate mofetil; Drug: Tacrolimus; Biological: Belatacept; Drug: methylprednisolone

Study type: Interventional

Funder types: NETWORK; Industry; NIH

Identifiers

NCT01790594

U01AI084150 (U.S. NIH Grant/Contract)

SDY1433 (Other Identifier)

DAIT CTOT-15

NIAID CRMS ID#: 20117 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other anti-rejection medications necessary and thereby reduce the long-term side effects caused by the other medications. The researchers also want to learn more about the safety of this treatment and long term health of transplanted pancreases and kidneys.

Full description

Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term.

Enrollment: 46 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Ability to understand and provide written informed consent;
• Candidate for a primary simultaneous kidney and pancreas allograft with random c-peptide <0.3 ng/mL;
• No known contraindications to study therapy using NULOJIX® (belatacept);
• Female subjects 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 study completion;
• No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
• Negative crossmatch, actual or virtual, or a Panel Reactive Antibodies (PRA) of 0% on historic and admission sera, as determined by each participating study center;
• A documented negative Tuberculosis (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 transplantation other than a kidney and pancreas;
• Recipient of previous organ transplant;
• Epstein-Barr Virus (EBV) sero-negative recipients or recipients whose EBV serostatus is unknown prior to the time of transplantation;
• Individuals infected by the hepatitis B or C viruses or HIV;
• Individuals who have required treatment with systemic prednisone or other immunosuppressive drugs within 1 year prior to transplant;
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 2 patient groups

Immunosuppression without Belatacept

Active Comparator group

Description:

Induction: 5 day course of methylprednisolone or equivalent; Induction: Anti-thymocyte Globulin (Rabbit); Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter. Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).

Treatment:

Drug: methylprednisolone

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Biological: Anti-thymocyte Globulin (Rabbit)

Immunosuppression Including Belatacept

Experimental group

Description:

Induction: 5 day course of methylprednisolone or equivalent; Induction: Anti-thymocyte Globulin (Rabbit); Maintenance Immunosuppression: Belatacept Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below. Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).

Treatment:

Drug: methylprednisolone

Biological: Belatacept

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Biological: Anti-thymocyte Globulin (Rabbit)