Regimen Optimization Study

Bristol-Myers Squibb58 enrolled

Overview

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.

Calcineurin inhibitor (CNI)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Kidney Transplantation

Interventions

ThymoglobulinDRUG

BelataceptDRUG

mycophenolate mofetil(MMF)DRUG

CorticosteroidsDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (20)

California Institute Of Renal Research

San Diego, California, United States

Outcomes

Primary Outcomes

Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months

Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months

Time frame: 6 Months

Secondary Outcomes

Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 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 frame: Up to 24 Months

Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR).

Time to Clinically suspected biopsy proven acute rejection

Time frame: Up to 24 Months

Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection

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)

Time frame: At 6, 12 and 24 Months

Treatment Differences in Therapeutic Modalities

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.

Data from ClinicalTrials.gov

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California Pacific Medical Center

San Francisco, California, United States

University Of Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Emory Univeristy

Atlanta, Georgia, United States

University Of Illinois

Chicago, Illinois, United States

Tulane Medical Center

New Orleans, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

...and 10 more locations

Time frame: at 6, 12 and 24 Months

Number of Participants Who Survive With a Functioning Graft

Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant

Time frame: At 6, 12 and 24 months

Number of Participants Deaths Post Transplant

Number of participant deaths at 6, 12 and 24 months post transplant

Time frame: up to 24 months

Number of Participants Who Experience Graft Loss Post Transplant

Number of all participants who experience graft loss at 6, 12 and 24 months post transplant

Time frame: At 6, 12 and 24 months

Time to Event: Graft Loss and Death

The Number of days to participant Graft Loss and death for any reason

Time frame: Up to 728 Days

Absolute Calculated Glomerular Filtration Rate (cGFR): Mean

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

Time frame: Up 24 Months post-transplant

Median Calculated Glomerular Filtration Rate (cGFR)

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

Time frame: Up 24 Months post-transplant

Mean Change From Month 3 in cGFR

The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant

Time frame: Up 24 Months post-transplant

Urine Protein Creatinine Ratio (UPr/Cr)

Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.

Time frame: Up 24 Months post-transplant

Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA)

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

Time frame: Up to 24 Months

Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA)

Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.

Time frame: Up to 24 Months

Percentage of Participants With Adverse Events (AEs)

Percentage of participants with AEs up to 24 months post-transplant

Time frame: Up to 24 months Post-Transplant

Percentage of Participants With Serious Adverse Events (SAEs)

Percentage of participants with SAEs up to 24 months post-transplant

Time frame: Up to 24 months Post-Transplant

Percentage of Participants With Events of Special Interest (ESIs)

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

Time frame: Up to 24 Months

Percentage of Particpants With Laboratory Test Abnormalities (LTAs)

Percentage of participants with laboratory tests with marked laboratory abnormalities

Time frame: At 24 Months

Mean and Mean Change From Baseline in Blood Glucose

Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant

Time frame: Up to 24 months

Mean and Mean Change From Baseline in Whole Blood HbA1c

Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.

Time frame: Up to 24 months

Percentage of Participants With New Onset Diabetes After Transplant

Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.

Time frame: up to 24 months

Absolute Values of Blood Pressure: Mean

Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

Time frame: Up to 24 Months

Absolute Values of Blood Pressure: Median

Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

Time frame: Up to 24 Months

Mean Changes From Baseline Values for Blood Pressure

Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant

Time frame: Up to 24 Months

Absolute Values of Fasting Lipid Values: Mean

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)

Time frame: Up to 24 Months

Absolute Values of Fasting Lipid Values: Median

Time frame: Up to 24 Months

Mean Changes From Baseline Values of Lipid Values

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)

Time frame: at months 12 and 24