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

NCT ID: NCT04849533

Last Updated: 2021-04-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-09

Study Completion Date

2024-07-31

Brief Summary

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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

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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

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Kidney Transplant Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group D Bela/EVR

rATG induction/belatacept/everolimus/early steroid withdrawal rATG 1.5mg/kg IV X 4 doses over 10 days belatacept 10mg/kg IV X 1 on POD 1, POD 5, weeks 2, 4, 8, and 12 then 5mg/kg IV X 1 on week 16 and then every 4 weeks thereafter Steroid taper x 5 days (500mg IV, 250mg IV, 125mg IV, 80mg po, 60mg po) Everolimus started within 24hours at 2mg BID and dosed to level 3-8ng/ml

Group Type EXPERIMENTAL

Belatacept

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

rabbit antithymocyte globulin

Intervention Type DRUG

rabbit antithymocyte globulin induction for prevention of rejection

Group E Bela/MMF

rATG induction/belatacept/mycophenolate/chronic steroidsrATG 1.5mg/kg IV X 4 doses over 10 days belatacept 10mg/kg IV X 1 on POD 1, POD 5, weeks 2, 4, 8, and 12 then 5mg/kg IV X 1 on week 16 and then every 4 weeks thereafter Steroid taper x 5 days (500mg IV, 250mg IV, 125mg IV, 80mg po, 60mg po) and then 5mg po daily thereafter MMF 1gm BID started pre-op and then continued throughout study

Group Type ACTIVE_COMPARATOR

Belatacept

Intervention Type DRUG

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

mycophenolate mofetil

Intervention Type DRUG

belatacept with mycophenolate is approved regimen for prevention of rejection

corticosteroids

Intervention Type DRUG

belatacept with chronic steroids is approved regimen for prevention of rejection

rabbit antithymocyte globulin

Intervention Type DRUG

rabbit antithymocyte globulin induction for prevention of rejection

Interventions

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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

Intervention Type 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

Intervention Type DRUG

mycophenolate mofetil

belatacept with mycophenolate is approved regimen for prevention of rejection

Intervention Type DRUG

corticosteroids

belatacept with chronic steroids is approved regimen for prevention of rejection

Intervention Type DRUG

rabbit antithymocyte globulin

rabbit antithymocyte globulin induction for prevention of rejection

Intervention Type DRUG

Other Intervention Names

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Nulojix Zortress Cellcept Prednisone rATG, thymoglobulin

Eligibility Criteria

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Inclusion Criteria

1. Male and female patients ≥ 18 years of age.
2. Patient who is receiving a renal transplant from a living or heart-beating deceased donor.
3. Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.
4. The patient has given written informed consent to participate in the study

Exclusion Criteria

1. Patient has previously received an organ transplant other than a kidney.
2. Patient is receiving an HLA identical living donor transplant.
3. Patient who is a recipient of a multiple organ transplant.
4. Patient has a most recent cytotoxic PRA of \>25% or calculated PRA \>50% where multiple moderate level HLA antibodies exist and in the opinion of the PI represents substantial HLA sensitization.
5. Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies.
6. Patient with a donor specific antibody (DSA) as deemed by the PI to be associated with significant risk of rejection.
7. Patient has received an ABO incompatible donor kidney.
8. The deceased donor and/or deceased donor kidney meet any of the following extended criteria for organ donation (ECD):

1. Donor age ≥ 60 years OR
2. Donor age 50-59 years and 1 of the following:

i. Cerebrovascular accident (CVA) + hypertension + SCr \> 1.5 mg/dL OR ii. CVA + hypertension OR iii. CVA + SCr \> 1.5 mg/dL OR iv. Hypertension + SCr \> 1.5 mg/dL OR c. CIT ≥ 24 hours, donor age \> 10 years OR d. Donation after cardiac death (DCD)
9. Recipients will be receiving a dual or en bloc kidney transplant.
10. Donor anticipated cold ischemia is \> 30 hours.
11. Recipient that is seropositive for hepatitis C virus (HCV) with detectable Hepatitis C viral load are excluded. HCV seropositive patients with a negative HCV viral load testing may be included.
12. Recipients receiving a kidney from a donor with HCV viremia (detected through nucleic acid testing or other means)
13. Recipients with a positive hepatitis B viral load or positive hepatitis B surface antigen testing within 1 year of consent.
14. Hepatitis B surface antibody negative recipients receiving a kidney from a donor seropositive for hepatitis B core antibody or hepatitis B nucleic acid.
15. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).
16. Recipient who is seronegative for Epstein Barr Virus (EBV)
17. Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
18. Patients with thrombocytopenia (PLT \<75,000/mm3), and/or leukopenia (WBC \< 2,000/mm3), or anemia (hemoglobin \< 6 g/dL) prior to study inclusion.
19. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.
20. Patient who has undergone desensitization therapy within 6 months prior to transplant.
21. Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil/mycophenolic acid, everolimus, rabbit anti-thymocyte globulin, or glucocorticoids.
22. Patient is receiving chronic steroid therapy at the time of transplant.
23. Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years, unless they have an expected disease-free survival of \>95%.
24. Patient is pregnant, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.
25. Women of childbearing potential must use reliable contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
26. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.
27. Inability to cooperate or communicate with the investigator.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Rita Alloway

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rita R Alloway, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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The Christ Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rita R Alloway, PharmD

Role: CONTACT

5135581568

Adele R Shields, PharmD

Role: CONTACT

5135852145

Facility Contacts

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Adele R Shields, PharmD

Role: primary

513-585-2145

Samantha Simmons

Role: backup

5135850016

Rita R Alloway, PharmD

Role: primary

513-558-1568

Other Identifiers

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IM103-423

Identifier Type: -

Identifier Source: org_study_id

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