Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Belatacept Early Steroid Withdrawal Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01729494
Recruitment Status : Completed
First Posted : November 20, 2012
Results First Posted : July 28, 2021
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
E. Steve Woodle, University of Cincinnati

Brief Summary:

The study purpose is to determine the safety and efficacy of a belatacept-based immunosuppressive regimen (calcineurin inhibitor free) with alemtuzumab or rabbit antithymocyte globulin (rATG) induction and early glucocorticoid withdrawal (CSWD) and a belatacept-based immunosuppressive regimen with tacrolimus-based regimen with rabbit antithymocyte globulin induction and early glucocorticoid withdrawal in renal transplant recipients.

The hypothesis is that a belatacept-based immunosuppressive regimen with alemtuzumab induction, mycophenolate mofetil (MMF)/mycophenolic acid (MPA), and early glucocorticoid withdrawal (Group A) in renal transplant recipients or Belatacept-based immunosuppressive regimen with rabbit antithymocyte globulin induction, MMF/MPA and early glucocorticoid withdrawal (Group B) will lead to less risk of graft loss, patient death, or reduced renal function at 12 months as compared to a tacrolimus-based immunosuppressive regimen with rabbit antithymocyte globulin, MMF/MPA, and early glucocorticoid withdrawal in renal transplant recipients (Group C).


Condition or disease Intervention/treatment Phase
Renal Transplantation Drug: Alemtuzumab Drug: rabbit antithymocyte globulin Drug: Belatacept Drug: Tacrolimus Drug: Mycophenolate mofetil Drug: early cessation of steroids Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 316 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Open Label, Multicenter Study of Belatacept-based Early Steroid Withdrawal Regimen With Alemtuzumab or rATG Induction Compared to Tacrolimus-based Early Steroid Withdrawal Regimen With rATG Induction in Renal Transplantation
Actual Study Start Date : September 2012
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A
Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids
Drug: Alemtuzumab
Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.
Other Name: Campath

Drug: Belatacept
Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is defined as the day of transplant.
Other Name: Nulojix

Drug: Mycophenolate mofetil
The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).
Other Name: Cellcept, various, Myfortic

Drug: early cessation of steroids

Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below:

Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids

Other Name: prednisone, various

Experimental: Group B
Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
Drug: rabbit antithymocyte globulin
Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
Other Name: Thymoglobulin

Drug: Belatacept
Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is defined as the day of transplant.
Other Name: Nulojix

Drug: Mycophenolate mofetil
The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).
Other Name: Cellcept, various, Myfortic

Drug: early cessation of steroids

Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below:

Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids

Other Name: prednisone, various

Active Comparator: Group C
Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
Drug: rabbit antithymocyte globulin
Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
Other Name: Thymoglobulin

Drug: Tacrolimus
Tacrolimus will be administered orally twice daily (BID). The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally. Tacrolimus should be started post-transplant within 48 hours or when serum creatinine drops lower than 4mg/dL, whichever comes first. The initial targeted trough level of tacrolimus will be 8 - 12 ng/mL for Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter.
Other Name: Prograf, various

Drug: Mycophenolate mofetil
The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).
Other Name: Cellcept, various, Myfortic

Drug: early cessation of steroids

Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below:

Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids

Other Name: prednisone, various




Primary Outcome Measures :
  1. # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min [ Time Frame: 12 months ]
    Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) < 45 mL/min


Secondary Outcome Measures :
  1. # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss) [ Time Frame: 24 months ]
    Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death

  2. # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months [ Time Frame: 24 months ]
    Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR < 45 ml/min/1.73m2

  3. eGFR (MRDRD) < 45 ml/Min/1.73m2 [ Time Frame: 24 months ]
    Patients with reduced Renal function measured by estimated GFR MDRD < 45 ml/min at 24 months

  4. Biopsy Proven Acute Rejection [ Time Frame: 24 months ]
    Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.

  5. Biopsy Proven Acute Cellular Rejection [ Time Frame: 24 months ]
    Biopsy proven acute cellular rejection (BPACR)

  6. Biopsy Proven Acute Antibody Mediated Rejection [ Time Frame: 24 months ]
    Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)

  7. Biopsy Proven Mixed Acute Rejection [ Time Frame: 24 months ]
    Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection

  8. # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant [ Time Frame: 24 months ]
    Number of patients (%) with development of denovo DSA after transplant

  9. Mean eGFR (MDRD) (ml/Min/1.73m2) [ Time Frame: 24 months ]
    Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint

  10. Proteinuria UPC Ratio > 0.8 [ Time Frame: 24 months ]
    Number of Patients with a Urine protein/creatinine (UPC) ratio > 0.8

  11. Patient Death [ Time Frame: 24 months ]
    Number of Patients who experienced death, all causes


Other Outcome Measures:
  1. Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR) [ Time Frame: 24 months ]
    Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection

  2. New Onset Diabetes After Transplantation (NODAT) [ Time Frame: 24 months ]
    Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included

  3. Time to First BPAR [ Time Frame: 24 months ]
    Mean Time to first episode of BPAR (days)

  4. # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade [ Time Frame: 24 months ]
    Number of patients with their First BPACR with a Banff grade >= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.

  5. Delayed Graft Function [ Time Frame: 24 months ]
    Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.

  6. Leukopenia (WBC < 2000/mm3) [ Time Frame: 24 months ]
    Number of patients developing leukopenia defined as WBC < 2000/mm3

  7. Steroid Therapy [ Time Frame: 24 months ]
    Number of patients on treatment with corticosteroids at 2 years

  8. Discontinuation of Mycophenolate [ Time Frame: 24 months ]
    Number of patients who were discontinued from mycophenolate treatment at 2 years

  9. Discontinuation of Study Treatment (Belatacept or Tacrolimus) [ Time Frame: 24 months ]
    Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients > 18 years of age.
  2. Patient who is receiving a renal transplant from a living or 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 human leucocyte antigen (HLA) identical living donor transplant.
  3. Patient who is a recipient of a multiple organ transplant.
  4. Patient has a most recent cytotoxic panel reactive antibody (PRA) of >25% or calculated PRA of > 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 local PI to be associated with significant risk of rejection.
  7. Patient has received a blood group (ABO) incompatible donor kidney.
  8. The donor and/or 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:

      • Cerebrovascular accident (CVA) + hypertension + serum creatinine (SCr) > 1.5 mg/dL OR
      • CVA + hypertension OR
      • CVA + SCr > 1.5 mg/dL OR
      • Hypertension + SCr > 1.5 mg/dL OR
    • Cold ischemia time (CIT) > 24 hours, donor age > 10 years OR
    • 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 who are Hepatitis B core antibody seropositive are eligible if their hepatitis B viral loads are negative. After transplant, their hepatitis B viral loads will be monitored every three months for the first year after transplant. If hepatitis B viral loads become positive, patients will be treated per institutional standard of care.
  13. Patients who are Hepatitis B surface antibody seropositive and who receive a kidney from a Hepatitis B core surface antibody positive donor may be included.
  14. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).
  15. Recipient who is seronegative for Epstein Barr virus (EBV).
  16. Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
  17. Patients with thrombocytopenia (PLT < 75,000/mm3), and/or leucopoenia (WBC < 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.
  18. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.
  19. Patient who has undergone desensitization therapy within 6 months prior to transplant.
  20. Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids.
  21. Patient is receiving chronic steroid therapy at the time of transplant.
  22. 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%.
  23. 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.
  24. Women of childbearing potential must use reliable contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
  25. 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.
  26. Inability to cooperate or communicate with the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01729494


Locations
Layout table for location information
United States, California
California Pacific Medical Center
San Francisco, California, United States, 94107
United States, Colorado
University of Colorado Denver
Denver, Colorado, United States, 80045
United States, Florida
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
University of Illinois Medical Center at Chicago
Chicago, Illinois, United States, 60612
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Ohio
The Christ Hospital
Cincinnati, Ohio, United States, 45219
University of Cincinnati
Cincinnati, Ohio, United States, 45219
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Cincinnati
Investigators
Layout table for investigator information
Principal Investigator: E. Steve Woodle, MD University of Cincinnati
  Study Documents (Full-Text)

Documents provided by E. Steve Woodle, University of Cincinnati:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: E. Steve Woodle, MD, FACS, University of Cincinnati
ClinicalTrials.gov Identifier: NCT01729494    
Other Study ID Numbers: BEST
First Posted: November 20, 2012    Key Record Dates
Results First Posted: July 28, 2021
Last Update Posted: July 28, 2021
Last Verified: August 2020
Keywords provided by E. Steve Woodle, University of Cincinnati:
belatacept
rabbit antithymocyte globulin
alemtuzumab
corticosteroid withdrawal
Additional relevant MeSH terms:
Layout table for MeSH terms
Mycophenolic Acid
Prednisone
Alemtuzumab
Abatacept
Tacrolimus
Thymoglobulin
Antilymphocyte Serum
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Antirheumatic Agents