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Regimen Optimization Study

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: NCT02137239
Recruitment Status : Completed
First Posted : May 13, 2014
Results First Posted : June 22, 2021
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
Patients who undergo a kidney transplant require prolonged therapy with drugs that suppress the immune system (called immunosuppressive regimens) to stop the immune system from attacking the transplanted kidney in order to limit damage to or the possibility of rejecting the transplanted kidney. The purpose of this study is to evaluate benefits and risks of two immunosuppressive regimens (belatacept with everolimus or tacrolimus with mycophenolate mofetil) following thymoglobulin induction and rapid corticosteroid withdrawal.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Drug: Thymoglobulin Drug: Belatacept Drug: mycophenolate mofetil(MMF) Drug: Corticosteroids Drug: Everolimus(EVL) Drug: Tacrolimus(TAC) Phase 2

Detailed Description:
Calcineurin inhibitor (CNI)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression
Actual Study Start Date : December 31, 2015
Actual Primary Completion Date : May 2, 2019
Actual Study Completion Date : May 2, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Belatacept

Arm Intervention/treatment
Experimental: Belatacept + Everolimus
Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)
Drug: Thymoglobulin
Other Name: ATG

Drug: Belatacept
Other Name: Nulojix

Drug: Corticosteroids
Other Names:
  • Methylprednisolone
  • Prednisone

Drug: Everolimus(EVL)
Other Names:
  • Certican®
  • Zortress®

Experimental: Tacrolimus + Mycophenolate mofetil
Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)
Drug: Thymoglobulin
Other Name: ATG

Drug: mycophenolate mofetil(MMF)
Other Name: CellCept

Drug: Corticosteroids
Other Names:
  • Methylprednisolone
  • Prednisone

Drug: Tacrolimus(TAC)
Other Name: Prograf




Primary Outcome Measures :
  1. Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months [ Time Frame: 6 Months ]
    Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months


Secondary Outcome Measures :
  1. Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months [ Time Frame: Up to 24 Months ]

    Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months

    Change in the incidence of CSBPAR at 6, 12 and 24 months post transplant, in the belatacept + EVL(Treatment A) as compared to TAC + MMF (Treatment B).


  2. Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR). [ Time Frame: Up to 24 Months ]
    Time to Clinically suspected biopsy proven acute rejection

  3. Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection [ Time Frame: At 6, 12 and 24 Months ]

    Treatment differences in the severity grades to treat all episodes of CSBPAR at 6, 12, and 24 months post-transplant.

    Type 1A - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/Tubular cross section or group of 10 Tubular cell). Type 1B - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/Tubular cross section or group of 10 Tubular cell).Type 2A - Cases with mild to moderate intimal arteritis.Type 2B - Cases with severe intimal arteritis comprising >25% of the luminal area. Type 3 - Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (v3 with accompanying lymphocytic inflammation)


  4. Treatment Differences in Therapeutic Modalities [ Time Frame: at 6, 12 and 24 Months ]
    Treatment Received for Biopsy Proven Acute Rejection (Banff Grade IA or Higher), or Humoral (Antibody Mediated) Rejection Treatment regimen: Categorical analysis of CSBPAR episodes by treatment received.

  5. Number of Participants Who Survive With a Functioning Graft [ Time Frame: At 6, 12 and 24 months ]
    Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant

  6. Number of Participants Deaths Post Transplant [ Time Frame: up to 24 months ]
    Number of participant deaths at 6, 12 and 24 months post transplant

  7. Number of Participants Who Experience Graft Loss Post Transplant [ Time Frame: At 6, 12 and 24 months ]
    Number of all participants who experience graft loss at 6, 12 and 24 months post transplant

  8. Time to Event: Graft Loss and Death [ Time Frame: Up to 728 Days ]
    The Number of days to participant Graft Loss and death for any reason

  9. Absolute Calculated Glomerular Filtration Rate (cGFR): Mean [ Time Frame: Up 24 Months post-transplant ]
    Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula

  10. Median Calculated Glomerular Filtration Rate (cGFR) [ Time Frame: Up 24 Months post-transplant ]
    Median cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula

  11. Mean Change From Month 3 in cGFR [ Time Frame: Up 24 Months post-transplant ]
    The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant

  12. Urine Protein Creatinine Ratio (UPr/Cr) [ Time Frame: Up 24 Months post-transplant ]
    Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.

  13. Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA) [ Time Frame: Up to 24 Months ]
    Percentage of participants with, and titers of pre-existing (pre-transplant) DSA on Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 posttransplant

  14. Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA) [ Time Frame: Up to 24 Months ]
    Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.

  15. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to 24 months Post-Transplant ]
    Percentage of participants with AEs up to 24 months post-transplant

  16. Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 24 months Post-Transplant ]
    Percentage of participants with SAEs up to 24 months post-transplant

  17. Percentage of Participants With Events of Special Interest (ESIs) [ Time Frame: Up to 24 Months ]

    Percentage of participants which have one of the following events of special interest:

    Serious Infections Post-Transplant Lymphoproliferative Disorder (PTLD) Progressive multifocal leukoencephalopathy (PML) Malignancies (Other than PTLD) including non-melanoma skin carcinomas (Malignancies) Tuberculosis Infections Central Nervous System (CNS) Infections Viral Infections Infusion Related reactions within 24 hours since belatacept infusion


  18. Percentage of Particpants With Laboratory Test Abnormalities (LTAs) [ Time Frame: At 24 Months ]
    Percentage of participants with laboratory tests with marked laboratory abnormalities

  19. Mean and Mean Change From Baseline in Blood Glucose [ Time Frame: Up to 24 months ]
    Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant

  20. Mean and Mean Change From Baseline in Whole Blood HbA1c [ Time Frame: Up to 24 months ]
    Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.

  21. Percentage of Participants With New Onset Diabetes After Transplant [ Time Frame: up to 24 months ]
    Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.

  22. Absolute Values of Blood Pressure: Mean [ Time Frame: Up to 24 Months ]
    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

  23. Absolute Values of Blood Pressure: Median [ Time Frame: Up to 24 Months ]
    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

  24. Mean Changes From Baseline Values for Blood Pressure [ Time Frame: Up to 24 Months ]
    Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant

  25. Absolute Values of Fasting Lipid Values: Mean [ Time Frame: Up to 24 Months ]

    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following:

    Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)


  26. Absolute Values of Fasting Lipid Values: Median [ Time Frame: Up to 24 Months ]

    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following:

    Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)


  27. Mean Changes From Baseline Values of Lipid Values [ Time Frame: at months 12 and 24 ]

    Mean changes from baseline values in the following:

    Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)




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.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Men and women, aged 18 to 75
  • Serologic test results are positive for past exposure to Epstein Barr Virus (EBV+)
  • Diagnosed with end stage renal disease (ESRD) and scheduled to undergo transplantation of a non-HLA identical, living or standard criteria deceased donor kidney

Exclusion Criteria:

  • Primary cause of ESRD is: primary focal segmental glomerulosclerosis; or Type I or II membranoproliferative glomerulonephritis; or Hemolytic Uremic Syndrome / Thrombotic Thrombocytopenic Purpura
  • Had a previous graft loss due to acute rejection
  • At increased immunologic risk of graft loss due to panel reactive antibodies (PRA) >20% or need for desensitization therapy
  • Scheduled to receive a: kidney from identical twin; or paired kidney; or kidney from a Cytomegalovirus(CMV) positive donor when recipient is CMV negative; or kidney from an extended criteria donor
  • Have a body mass index (BMI) of > 35 kg/m2 for nondiabetics or > 30 kg/m2 for diabetics
  • Diagnosed as Hepatitis B positive; or Hepatitis C positive; or HIV positive; or currently or previously active or inadequately treated latent

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): NCT02137239


Locations
Show Show 20 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] August 14, 2017
Statistical Analysis Plan  [PDF] June 26, 2019

Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02137239    
Other Study ID Numbers: IM103-177
2013-002090-21 ( EudraCT Number )
First Posted: May 13, 2014    Key Record Dates
Results First Posted: June 22, 2021
Last Update Posted: June 22, 2021
Last Verified: May 2021
Additional relevant MeSH terms:
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Mycophenolic Acid
Prednisone
Methylprednisolone
Everolimus
Abatacept
Tacrolimus
Thymoglobulin
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
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents