NCT04849533

Belatacept With Early Steroid Withdrawal rATG and Everolimus in Renal Transplantation (BETTER Trial)

A Randomized, Multicenter Study of Belatacept, Everolimus, rATG and Early Steroid Withdrawal Versus Belatacept, Mycophenolate, rATG and Chronic Steroids in Renal Transplantation

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: University of Cincinnati · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to determine the safety and efficacy of two calcineurin inhibitor free treatment groups 1) a belatacept, everolimus and early corticosteroid withdrawal (ECSWD) immunosuppressive regimen with rabbit antithymocyte globulin induction (rATG) and 2) a belatacept, mycophenolate, chronic steroid regimen with rATG and compare to historical controls of tacrolimus-based and belatacept-based regimens in combination with rATG induction, mycophenolate, and ESWD in renal transplant recipients. The purpose is to evaluate the effect of 2 regimens (rATG induction/belatacept/everolimus/ESWD and rATG induction/belatacept/mycophenolate/CS) on the composite of patient death, graft loss, or eGFR (MDRD) \< 45 mL/min/1.73m2 at Month 12 post-transplantation compared to historical controls of the BEST Trial (groups B and C).

Detailed description

The BETTER trial is designed to determine the safety and efficacy of two calcineurin inhibitor free treatment groups 1) a belatacept, everolimus and early corticosteroid withdrawal (ESWD) immunosuppressive regimen with rabbit antithymocyte globulin induction (rATG) and 2) a belatacept, mycophenolate, chronic steroid regimen with rATG and compare to historical controls of tacrolimus-based and belatacept-based regimens in combination with rATG induction, mycophenolate, and ESWD in renal transplant recipients. Study Hypotheses 1. A belatacept-based immunosuppressive regimen with rATG induction, everolimus and ESWD in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a tacrolimus-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group C). 2. A belatacept-based immunosuppressive regimen with rATG induction, everolimus and ESWD in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a belatacept-based immunosuppressive regimen with rATG and mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group B). 3. A belatacept-based immunosuppressive regimen with rATG, mycophenolate and CS in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a tacrolimus-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group C). 4. A belatacept-based immunosuppressive regimen with rATG induction, mycophenolate and CS in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a belatacept-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group B). A controlled, randomized group study is accepted in renal transplantation to evaluate new immunosuppressive regimens versus the current standard of care. Although the ideal study would employ a blinded methodology with a simultaneous control group to minimize bias, the study will not be blinded and evaluates a historical control groups conducted in similar centers. To allow comparison between studies, the primary composite endpoint of death, graft loss, or eGFR \<45ml/min/1.73m2 will be analyzed similarly. The secondary and tertiary endpoints are the similar as well. The BETTER study proposes to compare two additional treatment groups of rATG/belatacept/everolimus/ESWD (Group D) and rATG/belatacept/mycophenolate/CS (Group E) to the historical control Groups B and C. All immunosuppressive agents are approved by the FDA for the prophylaxis of renal transplant rejection, and will be dosed and administered consistent with current clinical practice.

Conditions

• Kidney Transplant Rejection

Interventions

Type	Name	Description
DRUG	Belatacept	belatacept with everolimus is experimental regimen and it is compared to the labeled regimen of belatacept with mycophenolate with steroids for prevention of rejection in renal transplant recipients
DRUG	Everolimus	belatacept with everolimus is experimental regimen and it is compared to the labeled regimen of belatacept with mycophenolate with steroids for prevention of rejection in renal transplant recipients
DRUG	mycophenolate mofetil	belatacept with mycophenolate is approved regimen for prevention of rejection
DRUG	corticosteroids	belatacept with chronic steroids is approved regimen for prevention of rejection
DRUG	rabbit antithymocyte globulin	rabbit antithymocyte globulin induction for prevention of rejection

Timeline

• Start date: 2021-04-09
• Primary completion: 2023-07-01
• Completion: 2024-07-01
• First posted: 2021-04-19
• Last updated: 2021-04-19

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study