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.
Brief Title
Regimen Optimization Study
Detailed Description
Calcineurin inhibitor (CNI)
Completion Date
Completion Date Type
Actual
Conditions
Kidney Transplantation
Eligibility Criteria
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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
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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT02137239
Org Class
Industry
Org Full Name
Bristol-Myers Squibb
Org Study Id
IM103-177
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression
Primary Outcomes
Outcome Description
Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months
Outcome Measure
Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months
Outcome Time Frame
6 Months
Secondary Ids
Secondary Id
2013-002090-21
Secondary Outcomes
Outcome Description
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).
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).
Outcome Time Frame
Up to 24 Months
Outcome Measure
Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months
Outcome Description
Time to Clinically suspected biopsy proven acute rejection
Outcome Time Frame
Up to 24 Months
Outcome Measure
Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR).
Outcome Description
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)
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)
Outcome Time Frame
At 6, 12 and 24 Months
Outcome Measure
Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection
Outcome Description
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.
Outcome Time Frame
at 6, 12 and 24 Months
Outcome Measure
Treatment Differences in Therapeutic Modalities
Outcome Description
Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant
Outcome Time Frame
At 6, 12 and 24 months
Outcome Measure
Number of Participants Who Survive With a Functioning Graft
Outcome Description
Number of participant deaths at 6, 12 and 24 months post transplant
Outcome Time Frame
up to 24 months
Outcome Measure
Number of Participants Deaths Post Transplant
Outcome Description
Number of all participants who experience graft loss at 6, 12 and 24 months post transplant
Outcome Time Frame
At 6, 12 and 24 months
Outcome Measure
Number of Participants Who Experience Graft Loss Post Transplant
Outcome Description
The Number of days to participant Graft Loss and death for any reason
Outcome Time Frame
Up to 728 Days
Outcome Measure
Time to Event: Graft Loss and Death
Outcome Description
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
Outcome Time Frame
Up 24 Months post-transplant
Outcome Measure
Absolute Calculated Glomerular Filtration Rate (cGFR): Mean
Outcome Description
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
Outcome Time Frame
Up 24 Months post-transplant
Outcome Measure
Median Calculated Glomerular Filtration Rate (cGFR)
Outcome Description
The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant
Outcome Time Frame
Up 24 Months post-transplant
Outcome Measure
Mean Change From Month 3 in cGFR
Outcome Description
Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Outcome Time Frame
Up 24 Months post-transplant
Outcome Measure
Urine Protein Creatinine Ratio (UPr/Cr)
Outcome Description
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
Outcome Time Frame
Up to 24 Months
Outcome Measure
Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA)
Outcome Description
Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.
Outcome Time Frame
Up to 24 Months
Outcome Measure
Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA)
Outcome Description
Percentage of participants with AEs up to 24 months post-transplant
Outcome Time Frame
Up to 24 months Post-Transplant
Outcome Measure
Percentage of Participants With Adverse Events (AEs)
Outcome Description
Percentage of participants with SAEs up to 24 months post-transplant
Outcome Time Frame
Up to 24 months Post-Transplant
Outcome Measure
Percentage of Participants With Serious Adverse Events (SAEs)
Outcome Description
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
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
Outcome Time Frame
Up to 24 Months
Outcome Measure
Percentage of Participants With Events of Special Interest (ESIs)
Outcome Description
Percentage of participants with laboratory tests with marked laboratory abnormalities
Outcome Time Frame
At 24 Months
Outcome Measure
Percentage of Particpants With Laboratory Test Abnormalities (LTAs)
Outcome Description
Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant
Outcome Time Frame
Up to 24 months
Outcome Measure
Mean and Mean Change From Baseline in Blood Glucose
Outcome Description
Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.
Outcome Time Frame
Up to 24 months
Outcome Measure
Mean and Mean Change From Baseline in Whole Blood HbA1c
Outcome Description
Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.
Outcome Time Frame
up to 24 months
Outcome Measure
Percentage of Participants With New Onset Diabetes After Transplant
Outcome Description
Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Outcome Time Frame
Up to 24 Months
Outcome Measure
Absolute Values of Blood Pressure: Mean
Outcome Description
Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Outcome Time Frame
Up to 24 Months
Outcome Measure
Absolute Values of Blood Pressure: Median
Outcome Description
Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant
Outcome Time Frame
Up to 24 Months
Outcome Measure
Mean Changes From Baseline Values for Blood Pressure
Outcome Description
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)
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Outcome Time Frame
Up to 24 Months
Outcome Measure
Absolute Values of Fasting Lipid Values: Mean
Outcome Description
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)
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Outcome Time Frame
Up to 24 Months
Outcome Measure
Absolute Values of Fasting Lipid Values: Median
Outcome Description
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)
Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Outcome Time Frame
at months 12 and 24
Outcome Measure
Mean Changes From Baseline Values of Lipid Values
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Liise Kayler
Investigator Email
lkayler@montefiore.org
Investigator Phone