Mechanisms of Belatacept Effect on Alloimmunity and Antiviral Response After Kidney Transplantation (BMS IM 103-309)

• Status: Completed
• Trial end date: 2021-04-21
• Target enrollment: 0
• Participant gender: All

Summary

This research evaluates the effectiveness of a new drug called belatacept (Nulojix) for the prevention of acute rejection and preservation of kidney function in transplant patients. Belatacept was approved in 2011 by the United States Food and Drug Administration (FDA) and is being marketed as Nulojix. The pharmaceutical company sponsoring this study is Bristol-Myers Squibb.

Belatacept is a prescription medicine used in adults to prevent transplant rejection in people who have received a kidney transplant. Transplant rejection happens when the body's immune system senses that the new transplanted kidney is different or foreign, and attacks it. Belatacept is used with corticosteroids and certain other medicines to help prevent rejection of your new kidney.

The purpose of the research is to understand whether the new drug, belatacept, is better than other anti-rejection drugs, such as cyclosporine and tacrolimus that are typically used in the treatment against kidney rejection in transplant patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborator: Bristol-Myers Squibb
• Treatments: Abatacept; Antiviral Agents

Criteria

Inclusion Criteria:

1. The subject is willing to provide signed written informed consent Target Population

2. The subject is a first-time recipient of a living or deceased donor kidney transplant

3. Evidence of calcineurin inhibitor side effects during the first 3 months after transplant as defined as

1. Neurologic toxicity, defined as tremor, altered mental status, or seizure 2. Renal toxicity, defined as GFR <60 3. Metabolic toxicity, defined as a new requirement for medication to control hyperglycemia 4. Hematologic toxicity, defined as development of thrombotic microangiopathy Age and Gender 4) Men and women, ages 18 and older, inclusive 5) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Refer to the protocol for details regarding description and handling of WOCBP subjects.

WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of study medication then every 3 months during the period of study participation.

6) Men must use an adequate method of contraception throughout the study, and for up to 8 weeks after the last infusion, so that the risk of pregnancy to their partners is minimized.

7) MMF must be dosed at 500 mg by mouth twice daily or greater at the time of study entry 8) Prednisone must be dosed at >=10 mg by mouth daily for patients less than 6 weeks post-transplantation, and at >=5mg by mouth daily for patients greater than 6 weeks post-transplantation at the time of study entry.

Exclusion Criteria:

1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last infusion.

2. Women who are pregnant or breastfeeding

3. Women with a positive pregnancy test on enrollment or prior to study drug administration

4. Males unwilling or unable to use an adequate method of contraception for the entire study period and for up to 8 weeks after the last infusion of study medication Immunologic status

5. Subjects with PRA ≥ 30% at time of transplant

6. Subjects with zero HLA antigen mismatched donors (either from related or unrelated donor)

7. Subjects with any prior solid organ transplant (including kidney)

8. Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant

9. Subjects with a history of biopsy-proven acute rejection post-transplant (humoral or cellular) in the first three months post transplantation Infection related risks

10. Subjects who are hepatitis C antibody-positive or polymerase chain reaction (PCR)-positive for hepatitis C

11. Subjects who are hepatitis B surface antigen-positive or PCR-positive for hepatitis B

12. Subjects with known human immunodeficiency virus (HIV) infection

13. Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years or any subject who previously required triple (or more) combination therapy for TB.

14. Subjects who are EBV antibody negative and have received grafts from EBV antibody positive donors.

Prohibited Therapies and/or Medications

15. Subjects who have used any investigational drug within 30 days prior to the Day 1 visit

16. Subjects previously treated with belatacept 18) Use of mTOR inhibitors at any time after transplantation