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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

Tracking Information
First Submitted Date  ICMJE May 12, 2014
First Posted Date  ICMJE May 13, 2014
Results First Submitted Date  ICMJE October 14, 2020
Results First Posted Date  ICMJE June 22, 2021
Last Update Posted Date June 22, 2021
Actual Study Start Date  ICMJE December 31, 2015
Actual Primary Completion Date May 2, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2021)
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 12, 2014)
Incidence of clinically-suspected biopsy-proven acute rejection (CSBPAR) [ Time Frame: Up to 6 months post-transplantation ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2021)
  • 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).
  • Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR). [ Time Frame: Up to 24 Months ]
    Time to Clinically suspected biopsy proven acute rejection
  • 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)
  • 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.
  • 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
  • Number of Participants Deaths Post Transplant [ Time Frame: up to 24 months ]
    Number of participant deaths at 6, 12 and 24 months post transplant
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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.
  • 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
  • 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
  • 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
  • Percentage of Particpants With Laboratory Test Abnormalities (LTAs) [ Time Frame: At 24 Months ]
    Percentage of participants with laboratory tests with marked laboratory abnormalities
  • 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
  • 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.
  • 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.
  • 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;
  • 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;
  • 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
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2014)
  • Acute rejection [ Time Frame: At 6, 12 and 24 months post-transplant ]
    Incidence of CSBPAR by 12 and 24 months post-transplantation, difference in the incidence of CSBPAR between arms by 6, 12 and 24 months posttransplantation, time to CSBPAR, severity (Banff grades) and treatment (corticosteroids only, T-Cell Depleting Therapies, other) of CSBPAR by 6, 12, and 24 months post-transplantation
  • Subject and graft survival [ Time Frame: At 6, 12, 24 months post-transplant ]
    Proportion of subjects who survive with a functioning graft at 6, 12 and 24 months post-transplant, proportion of subjects who experience death by 6, 12 and 24 months post-transplant, proportion of subjects who experience graft loss by 6, 12 and 24 months post-transplant, and time to death and graft loss
  • Renal Function [ Time Frame: 3, 6, 12 and 24 months post-transplant ]
    Absolute values and mean changes in calculated glomerular filtration rate (cGFR) by modification of diet in renal disease (study) (MDRD) formula
  • Donor Specific Anti-HLA Antibodies (DSA) [ Time Frame: Day 1 and by 12 and 24 months post-transplantation ]
    Incidence and level of pre-existing and de novo DSA
  • Safety and tolerability of each treatment regimen [ Time Frame: Up to 56 days after last dose date (approximate treatment duration 24 months) ]
    Incidence of all adverse events (AEs) and serious AEs (SAEs) by 6, 12, and 24 months post-transplantation, incidence of events of special interest (ESI) at 6 months, 12 months, and 24 months, description and incidence of clinically significant changes in vital signs, and description and incidence of laboratory test abnormalities
  • Cardiovascular and metabolic co-morbidities [ Time Frame: Baseline (Day 1), 6, 12 and 24 months post-transplant ]
    Incidence of new onset diabetes after transplant (NODAT) by 6, 12, and 24 months post-transplantation, absolute values and mean change in systolic and diastolic blood pressure from baseline to month 6, month 12 and month 24, absolute values and mean change in lipid parameters from baseline to month 12 and month 24: Total serum cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regimen Optimization Study
Official Title  ICMJE Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression
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.
Detailed Description Calcineurin inhibitor (CNI)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Kidney Transplantation
Intervention  ICMJE
  • Drug: Thymoglobulin
    Other Name: ATG
  • Drug: Belatacept
    Other Name: Nulojix
  • Drug: mycophenolate mofetil(MMF)
    Other Name: CellCept
  • Drug: Corticosteroids
    Other Names:
    • Methylprednisolone
    • Prednisone
  • Drug: Everolimus(EVL)
    Other Names:
    • Certican®
    • Zortress®
  • Drug: Tacrolimus(TAC)
    Other Name: Prograf
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Belatacept
    • Drug: Corticosteroids
    • Drug: Everolimus(EVL)
  • 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)
    Interventions:
    • Drug: Thymoglobulin
    • Drug: mycophenolate mofetil(MMF)
    • Drug: Corticosteroids
    • Drug: Tacrolimus(TAC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2021)
58
Original Estimated Enrollment  ICMJE
 (submitted: May 12, 2014)
240
Actual Study Completion Date  ICMJE May 2, 2019
Actual Primary Completion Date May 2, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   United States
Removed Location Countries Austria,   Colombia,   Germany
 
Administrative Information
NCT Number  ICMJE NCT02137239
Other Study ID Numbers  ICMJE IM103-177
2013-002090-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP