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

NCT04849533 | Unknown Phase 4 FDA Drug

• 1 other identifier: IM103-423
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Kidney Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of patient death, graft loss, or eGFR (MDRD) < 45ml/min mL/min/1.73m2

  Number of subjects with composite endpoint of either 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).

  12 months

Secondary Outcomes (6)

• Incidence of Biopsy-proven acute rejection (BPAR) by Banff 2007 criteria stratified by type (ACR, AMR, or Mixed rejection)

  12 and 24 months

• Incidence of graft survival censored by patients who died with functioning graft

  12 and 24 months

• # of Patients with eGFR (MDRD) < 30 mL/min/1.73m2

  12 and 24 months

• # Patients with development of de novo donor specific antibody (DSA)

  12 and 24 months

• Composite endpoint of patient death, graft loss, or estimated eGFR (MDRD) < 45 mL/min/1.73m2 at Month 24 post-transplantation

  24 months

Study Arms (2)

Group D Bela/EVR

EXPERIMENTAL

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

Drug: Belatacept; Drug: Everolimus; Drug: rabbit antithymocyte globulin

Group E Bela/MMF

ACTIVE COMPARATOR

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

Drug: Belatacept; Drug: mycophenolate mofetil; Drug: corticosteroids; Drug: rabbit antithymocyte globulin

Interventions

Belatacept 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

Also known as: Nulojix

Group D Bela/EVR; Group E Bela/MMF

Everolimus 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

Also known as: Zortress

Group D Bela/EVR

mycophenolate mofetil DRUG

belatacept with mycophenolate is approved regimen for prevention of rejection

Also known as: Cellcept

Group E Bela/MMF

corticosteroids DRUG

belatacept with chronic steroids is approved regimen for prevention of rejection

Also known as: Prednisone

Group E Bela/MMF

rabbit antithymocyte globulin DRUG

rabbit antithymocyte globulin induction for prevention of rejection

Also known as: rATG, thymoglobulin

Group D Bela/EVR; Group E Bela/MMF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥ 18 years of age.
• Patient who is receiving a renal transplant from a living or heart-beating deceased donor.
• The patient has given written informed consent to participate in the study

You may not qualify if:

• Patient has previously received an organ transplant other than a kidney.
• Patient is receiving an HLA identical living donor transplant.
• Patient who is a recipient of a multiple organ transplant.
• 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.
• Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies.
• Patient with a donor specific antibody (DSA) as deemed by the PI to be associated with significant risk of rejection.
• Patient has received an ABO incompatible donor kidney.
• The deceased donor and/or deceased donor kidney meet any of the following extended criteria for organ donation (ECD):
• Donor age ≥ 60 years OR
• 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)
• Recipients will be receiving a dual or en bloc kidney transplant.
• Donor anticipated cold ischemia is \> 30 hours.
• 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.
• Recipients receiving a kidney from a donor with HCV viremia (detected through nucleic acid testing or other means)

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (2)

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

MeSH Terms

Interventions

Abatacept; Everolimus; Mycophenolic Acid; Adrenal Cortex Hormones; Prednisone; thymoglobulin

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rita R Alloway, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rita R Alloway, PharmD

CONTACT

5135581568; rita.alloway@uc.edu

Adele R Shields, PharmD

CONTACT

5135852145; adele.rike@uc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: April 19, 2021
• Study Start: April 9, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2024
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)