Regimen Optimization Study

Kidney Transplantation Clinical Trial

Official title:

Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02137239
• Other study ID #: IM103-177
• Secondary ID: 2013-002090-21
• Status: Completed
• Phase: Phase 2
• Start date: December 31, 2015
• Est. completion date: May 2, 2019

Study information

• Verified date: May 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Calcineurin inhibitor (CNI)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: May 2, 2019
• Est. primary completion date: May 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Thymoglobulin

• Belatacept

• mycophenolate mofetil(MMF)

• Corticosteroids

• Everolimus(EVL)

• Tacrolimus(TAC)

Locations

Country	Name	City	State
Argentina	Clinica Privada Velez Sarsfield	Cordoba
Argentina	Sanatorio Parque S.A.	Rosario	Santa Fe
Argentina	Clinica De Nefrologia, Urologia Y Enf. Cardiovasculares	Sante Fe
United States	Emory Univeristy	Atlanta	Georgia
United States	University Of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Erie County Medical Center	Buffalo	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University Of Illinois	Chicago	Illinois
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Central PA Transplant Foundation	Harrisburg	Pennsylvania
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Tulane Medical Center	New Orleans	Louisiana
United States	California Institute Of Renal Research	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Swedish Medical Center - Swedish Colon and Rectal Clinic - First Hill (Northwest Colon and Rectal Cl	Seattle	Washington
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Wake Forest University School Of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 Months
Secondary	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).	Up to 24 Months
Secondary	Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR).	Time to Clinically suspected biopsy proven acute rejection	Up to 24 Months
Secondary	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)	At 6, 12 and 24 Months
Secondary	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.	at 6, 12 and 24 Months
Secondary	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	At 6, 12 and 24 months
Secondary	Number of Participants Deaths Post Transplant	Number of participant deaths at 6, 12 and 24 months post transplant	up to 24 months
Secondary	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	At 6, 12 and 24 months
Secondary	Time to Event: Graft Loss and Death	The Number of days to participant Graft Loss and death for any reason	Up to 728 Days
Secondary	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	Up 24 Months post-transplant
Secondary	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	Up 24 Months post-transplant
Secondary	Mean Change From Month 3 in cGFR	The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant	Up 24 Months post-transplant
Secondary	Urine Protein Creatinine Ratio (UPr/Cr)	Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.	Up 24 Months post-transplant
Secondary	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	Up to 24 Months
Secondary	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.	Up to 24 Months
Secondary	Percentage of Participants With Adverse Events (AEs)	Percentage of participants with AEs up to 24 months post-transplant	Up to 24 months Post-Transplant
Secondary	Percentage of Participants With Serious Adverse Events (SAEs)	Percentage of participants with SAEs up to 24 months post-transplant	Up to 24 months Post-Transplant
Secondary	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	Up to 24 Months
Secondary	Percentage of Particpants With Laboratory Test Abnormalities (LTAs)	Percentage of participants with laboratory tests with marked laboratory abnormalities	At 24 Months
Secondary	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	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	up to 24 months
Secondary	Absolute Values of Blood Pressure: Mean	Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;	Up to 24 Months
Secondary	Absolute Values of Blood Pressure: Median	Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;	Up to 24 Months
Secondary	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	Up to 24 Months
Secondary	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)	Up to 24 Months
Secondary	Absolute Values of Fasting Lipid Values: Median	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)	Up to 24 Months
Secondary	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)	at months 12 and 24

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting