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Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT) (BENEFIT)

Primary Purpose

Kidney Transplantation, Chronic Kidney Failure

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Cyclosporine (CsA)

Belatacept LI (less intensive)

Belatacept MI (more intensive)

About this trial

This is an interventional treatment trial for Kidney Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The subject is a recipient of a living donor or deceased donor kidney transplant. Male or Female, 18 or older Exclusion Criteria: First time recipient, PRA >- 50% or for retransplantation PRA >- 30%. If retransplantation, previous graft loss cannot be due to acute rejection. Positive cross match. Subject receiving extended criteria donor (ECD) organ For Long-term extension study-Subjects who have completed three years of study treatment (through Week 156)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Cyclosporine (CsA)

Belatacept LI (less intensive)

Belatacept MI (more intensive)

Arm Description

Outcomes

Primary Outcome Measures

Percent of Participants Surviving With a Functioning Graft by Month 12

Percent of Participants With a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or With a Decrease in mGFR Greater Than or Equal to 10 mL/Min/1.73m^2 From Month 3 to Month 12

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 mg/dL. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in SCr of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3.

Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12

Acute rejection was defined as a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence was defined if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. AR was defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted.

Secondary Outcome Measures

Mean Value of the Measured Glomerular Filtration Rate (mGFR)

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.

Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

Prevalence of CAN = if participant met any of the following conditions: a: CAN observed in a biopsy either prior to 12 months (including baseline biopsy) or first post 12 months biopsy; b: participant had graft loss during the first year post transplant; c: no biopsy was available post 12 months and CAN not observed in biopsies prior to 12 months, but the measured GFR from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2; d: no biopsy available either prior to or post 12 months, and the measured GFR (incorporated missing data imputation) from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2. CAN = All allograft biopsies evaluated for presence and severity of CAN by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Onset of CAN determined by the biopsy date when it was observed.

Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Number of Participants With Adverse Events of Special Interest by Month 84

Prospectively identified events of special interest which were a subset of all AEs, and were either SAEs or non-serious AEs, included the following categories: Serious Infections and Infestations, Thrombolic/embolic events, and Malignancy. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/ abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Time frame is from randomization to the event date, or to the last dose date+56, or to Month 84 (Day 2548), whichever is the earliest.

Mean Blood Pressure at Month 84

Blood pressure was measured in millimeters of mercury (mmHg). Blood pressure was measured soon after the participant arrived and sat quietly at rest for 10 minutes. 3 consecutive seated blood pressure readings were made at least 1 minute apart.

Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

Upper limit of normal (ULN). Units per Liter (U/L). Cells per microliter (c/µL). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).Cells per Liter (c/L). Milliequivalents/Liter (mEq/L). Hemoglobin (low): <8.0 g/dL; Platelet count: <50*10^9 c/L; Leukocytes: <2*10^3 c/µL; Alkaline phosphatase (ALP): >5.0*ULN U/L; Alanine aminotransferase (ALT): >5.0*ULN U/L; Asparate aminotransferase (AST): >5.0*ULN U/L; Bilirubin Total: >3.0*ULN mg/dL; Creatinine: >3.0*ULN mg/dL; Calcium Total: low if <7.0 mg/dL or high if >12.5 mg/dL; Bicarbonate: <11.0 mEq/L; Potassium serum: low if <3.0 mEq/L or high if >6.0 mEq/L; Magnesium serum: low is <0.8 mEq/L or high if >2.46 mEq/L; Sodium serum: low if <130.0 mEq/L or high if >155.0 mEq/L; Phosphorus inorganic: <2.0 mg/dL; Albumin: <2 g/dL; Uric acid: >10 mg/dL; Protein urine: >=3+

Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84

Only participants who had non-missing test result for Class I or Class II anti-donor HLA antibodies were included in analysis and only participants who had at least one non-NA test result or finding were counted. This was a cumulative summary (excluding baseline) and once a participant was positive, that participant remained positive for the later time point. Acute rejection (AR) defined: a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence defined: if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. AR defined as allograft biopsies of Banff 97 classification Grade IA or greater (higher scores indicate more severe rejection). Evaluated by blinded central independent pathologist.

Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.

Percent of Participants With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/Min/1.73m^2 From Month 3 to Month 12

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in serum creatinine (SCr) of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3. Month 3 = baseline

Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 milligrams per deciliter (mg/dL).

Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation

Calculated glomerular filtration rate (cGFR) was used to assess renal function (as measured by the estimated creatinine clearance) using the following modification of diet in renal disease (MDRD) formula: MDRD: GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant is female] x [1.180 if participant is black] x [BUN]^(-0.170) x [Alb]^(+0.318); Age in years; Alb = Albumin in g/dL; SCr = Serum creatinine in mg/dL; BUN = Blood urea nitrogen in mg/dL; cGFR = mL/min/1.73m2

Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12

Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36

The incidence of new onset diabetes mellitus defined as participants who developed diabetes mellitus after randomization and transplantation. Participants that did not have diabetes prior to randomization were determined to have new onset diabetes mellitus if (i) the participant received an anti-diabetic medication for a duration of at least 30 days or (ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is >=126 mg/dL (7.0 mmol/L). New onset diabetes mellitus (NODM) = post-transplant diabetes mellitus (PTDM)

Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

This analysis was based on all participants who had been followed up at least 1092 days after transplantation. Hypertension was defined in according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for participants with chronic kidney disease. This definition was based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. In addition, all participants who had a SBP < 130 mm Hg and a DBP < 80 mm Hg who received an antihypertensive medication(s) for the indication of hypertension or with a medical history of hypertension were included in this definition. Systolic blood pressure = SBP; Diastolic blood pressure = DBP

Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12

The incidence of hypertension was defined as the proportion of participants who developed hypertension after randomization and transplantation. Specifically, the incidence of hypertension was assessed only after the Week 4 visit. This period allowed for adequate stabilization and resolution of transient changes. If participants received antihypertensive medication for the indication of hypertension at this (or later) time point, they were considered to have developed hypertension. Hypertension was defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for subjects with chronic kidney disease. This definition was based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP

Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12

The prevalence of hypertension was defined as the proportion of participants at any given time who meet the definition of hypertension. Hypertension defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for participants with chronic kidney disease. This definition is based upon SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP

Mean Systolic Blood Pressure and Diastolic Blood Pressure

Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12

Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Participants with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP

Percent of Participants With Prevalence of Controlled Hypertension at Month 12

The prevalence of controlled hypertension was defined as the proportion of participants at any given time who met the definition of controlled hypertension. Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Participants with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP

Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12

Incidence of dyslipidemia was defined as the proportion of participants who developed dyslipidemia after randomization and transplantation. Dyslipidemia was defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia = hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). The TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.

Percent of Participants With Prevalence of Dyslipidemia at Month 12

The prevalence of dyslipidemia was defined as the proportion of participants at any given time who met the definition of dyslipidemia. Dyslipidemia defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.

Percent of Participants With Controlled Dyslipidemia at Month 12

Prevalence of controlled dyslipidemia = the proportion of participants at any given time who met the stated definition of dyslipidemia. Dyslipidemia defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). Controlled dyslipidemia defined as participants who received successful pharmacologic treatment for 1 of the above stated dyslipidemias, and their lipid values fell below the thresholds described. TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used.

Number of Participants With Antihyperlipidemic Medication by Intensity Level

An intensity level was associated with the dose level of the statin based anti-hyperlipidemic agent. Any other agent (i.e., non-statin therapy) used as an antihyperlipidemic were considered Level I treatment intensity. Multiple daily dose levels during a period were averaged to compute the daily dose during that period. Level I = 20 mg fluvastatin (flu), 10 mg lovastatin (lova), 10 mg pravastatin (prav), 5-10 mg simvastatin (sim); Level II = 10 mg atorvastatin (atorv), 40 mg flu, 20 mg lova, 20 mg prav, 5 mg rosuvastatin (rosu), 20 mg sim, 10/10 vytorin; Level III = 20 mg atorv, 80 mg flu, 40 mg lova, 40 mg prav, 10 mg rosu, 40 mg sim, 10/20 vytorin; Level IV = 40 mg atorv, 80 mg lova, 80 mg prav, 20 mg rosu, 80 mg sim, 10/40 vytorin; Level V = 80 mg atorv, 40 mg rosu, 10/80 vytorin. Concomitant use of a statin and an agent of another class elevated the intensity level of the statin therapy by 1 level; therefore, an intensity level of greater than V was possible.

Percent of Participants Using At Least One Anti-Hyperlipidemic Medication

This analysis is based on all participants who were followed up at least 1092 days after transplantation.

Mean Value of Lipid Parameters

Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides (TGs).

Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36

Prevalence of AR = participants with the stated definition of AR at any given time. AR defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted. Clinical evidence = if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification.

Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36

Acute rejection was defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined: if either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Only the episode with the highest Banff grade for each participant was counted.

Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

A participant was considered to have delayed graft function (DGF), if treated with dialysis within the first week (Day 1 - 8) after transplantation. The use of polyclonal antilymphocyte preparations (LDT) was permitted only for participants randomized to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated DGF following transplantation and were not permitted in belatacept-treated participants, except for the treatment of acute rejection. Participants treated with LDT began CsA at the discretion of the investigator by Day 7. LDT could also have been used in participants who met >= 1 of the following criteria, observed in the presence of a transplant artery and vein and no evidence of hydronephrosis by sonogram: Urine output < 250 mL/12 hours, no significant improvement (< 1 milligram per deciliter (mg/dL)) in serum creatinine from baseline value over the first 24 - 72 hours post-transplant, or dialysis treatment.

Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

The use of LDT (thymoglobulin or antithymocyte gamma globulin [ATGAM]) was permitted only for participants randomized to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated delayed graft function following transplantation. Acute rejection (AR) defined as a clinico-pathological event requiring clinical evidence (an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed) and biopsy confirmation. AR defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Only the episode with the highest Banff grade for each participant was counted.

Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36

Steroid-resistant acute rejection (AR) defined as the use of lymphocyte-depletion therapy following treatment with corticosteroids. AR defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined: either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 international standardized histopathological working classification of kidney transplant pathology. Only the episode with the highest Banff grade for each participant was counted.

Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12

Acute rejection (AR) = a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater. Clinical evidence = if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Complete recovery following AR defined as serum creatinine [SCr] levels returned to baseline. Recovery calculated using 2 algorithms: Algorithm 1 = last laboratory measurement prior to onset of AR (baseline and first laboratory measurement after 84 days since onset of AR = resolution); Algorithm 2 = lowest laboratory measurement on or after transplantation and prior to onset day of AR (baseline and lowest laboratory measurement after onset on first AR up to Month 12 = resolution)

Percent of Participants With Subclinical Rejection at Month 12

Subclinical rejection defined as histological findings by the central pathologist consistent with acute rejection, but lacking its clinical correlate. Acute rejection defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted. Clinical evidence defined if either a or b was satisfied: a) an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology.

Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36

Allograft rejection includes any episode of rejection including: clinically suspected rejection, treated rejection, any central biopsy-proven acute rejection (BPAR), and acute rejection (AR: a subset of BPAR) defined as central biopsy-proven rejection that was either clinically suspected by protocol-defined reasons or by other reasons and was treated. Acute rejection (AR) defined as a clinico-pathological event requiring clinical evidence ( either an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of AR) and renal biopsy confirmation biopsy demonstrating a Banff 97 working classification of kidney transplant pathology classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the highest Banff grade for each participant was counted.

Mean Value of Physical and Mental Components Using SF-36 Questionnaire

SF-36 was a Participant-Reported Quality of Life (QoL) Short Form (SF) questionnaire measuring health-related quality of life (HRQL) covering 2 scale measures: physical component summary (PCS) and mental component summary (MCS). PCS represented by 4 domains: physical function, role limitations due to physical problems, pain, and general health perception. MCS represented by 4 domains: vitality, social function, role limitations due to emotional problems, and mental health. Their scores were computed based on weighted combinations of the 8 domain scores, which were transformed to a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores reflect better health-related functional status. Scoring is standardized using the norm-based scoring method where data is scored in relation to the U.S. general population having a mean of 50 and a standard deviation of 10. Scores below 50 are below the U.S. general population norm and above 50 are above the U.S. general population norm.

Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire

Mean Relative to an Identified Distribution (Ridit) Value of Symptom Occurrence and Symptom Distress Using Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSDS-59R)

The Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) was used to assess the occurrence (never, occasionally, regularly, almost always, always) and distress (0=no distress to 4=terrible distress) of symptoms associated with immunosuppressive therapies. Ridit (relative to an identified distribution) analysis (Fleiss JL. Statistical methods for rates and proportions. New York: John Wiley & Sons, Inc. 1991) was used. Ridit scores were calculated at baseline and at 6, 12, 24, and 36 months for overall symptom occurrence score and overall symptom distress. The Ridit score reflects the probability that a score observed for an individual randomly selected from a group would be higher (worse symptom) than a score observed for a randomly selected individual from the reference group. The reference group was constituted by the frequency distribution of the responses of all participants on all items at baseline. The ridit of the reference group is by definition, 0.5.

Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36

Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36

Percent of Participants Surviving With a Functioning Graft

Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36

Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine (SCr) ≥ 6.0 milligrams per deciliter (mg/dL) or 530 micromoles per liter (μmol/L) as determined by the central laboratory for ≥ 4 weeks or ≥ 56 consecutive days of dialysis or impairment of renal function to such a degree that the participant underwent retransplant. Acute rejection was defined as central biopsy proven rejection that was either (1) clinically suspected by protocol defined reasons or (2) clinically suspected by other reasons and treated. Death and graft loss were not imputed.

Full Information

NCT ID

NCT00256750

First Posted

November 15, 2005

Last Updated

July 12, 2016

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00256750

Brief Title

Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)

Acronym

BENEFIT

Official Title

Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

March 2005 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to learn if Belatacept can provide protection from organ rejection following kidney transplantation while avoiding some of the toxic effects of standard immunosuppressive medications such as kidney damage. Effects on kidney function and patient survival as well as drug safety will also be studied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney Transplantation, Chronic Kidney Failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

738 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cyclosporine (CsA)

Arm Type

Active Comparator

Arm Title

Belatacept LI (less intensive)

Arm Type

Experimental

Arm Title

Belatacept MI (more intensive)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Cyclosporine (CsA)

Intervention Description

tablet, oral, 1st month target: 150-300 ng/mL, after 1st month target: 100-250 ng/mL, daily, 36 months (ST), 100-250 ng/mL, daily, 24 months (LT)

Intervention Type

Drug

Intervention Name(s)

Belatacept LI (less intensive)

Intervention Description

solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Intervention Type

Drug

Intervention Name(s)

Belatacept MI (more intensive)

Intervention Description

solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Primary Outcome Measure Information:

Title

Percent of Participants Surviving With a Functioning Graft by Month 12

Description

Time Frame

Day 1 to Month 12

Title

Description

Time Frame

Month 12; Month 3 to Month 12

Title

Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12

Description

Time Frame

Day 1 to Month 12

Secondary Outcome Measure Information:

Title

Mean Value of the Measured Glomerular Filtration Rate (mGFR)

Description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.

Time Frame

Months 3, 12, 24

Title

Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

Description

Time Frame

Month 12

Title

Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

Description

Time Frame

Randomization to Month 84

Title

Number of Participants With Adverse Events of Special Interest by Month 84

Description

Time Frame

Randomization to Month 84

Title

Mean Blood Pressure at Month 84

Description

Time Frame

Month 84

Title

Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

Description

Time Frame

Baseline to Month 36

Title

Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84

Description

Time Frame

Randomization to Month 84

Title

Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24

Description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2.

Time Frame

Month 3 to Month 12; Month 3 to Month 24

Title

Percent of Participants With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/Min/1.73m^2 From Month 3 to Month 12

Description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in serum creatinine (SCr) of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3. Month 3 = baseline

Time Frame

Month 3 to Month 12

Title

Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12

Description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 milligrams per deciliter (mg/dL).

Time Frame

Month 12

Title

Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation

Description

Time Frame

Months 6, 12, 24, 36

Title

Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12

Description

Time Frame

Month 6 to Month 12

Title

Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36

Description

Time Frame

Week 4 post-transplantation to Month 36

Title

Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

Description

Time Frame

Month 36

Title

Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12

Description

Time Frame

Month 12

Title

Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12

Description

Time Frame

Month 12

Title

Mean Systolic Blood Pressure and Diastolic Blood Pressure

Description

Time Frame

Months 12, 24, 36

Title

Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12

Description

Time Frame

Day 1 to Month 12

Title

Percent of Participants With Prevalence of Controlled Hypertension at Month 12

Description

Time Frame

Month 12

Title

Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12

Description

Time Frame

Randomization to Month 12

Title

Percent of Participants With Prevalence of Dyslipidemia at Month 12

Description

Time Frame

Month 12

Title

Percent of Participants With Controlled Dyslipidemia at Month 12

Description

Time Frame

Month 12

Title

Number of Participants With Antihyperlipidemic Medication by Intensity Level

Description

Time Frame

Month 36

Title

Percent of Participants Using At Least One Anti-Hyperlipidemic Medication

Description

This analysis is based on all participants who were followed up at least 1092 days after transplantation.

Time Frame

Month 36

Title

Mean Value of Lipid Parameters

Description

Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides (TGs).

Time Frame

Months 12, 24, 36

Title

Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36

Description

Time Frame

Randomization to Month 36

Title

Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36

Description

Time Frame

Randomization to Month 36

Title

Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

Description

Time Frame

Randomization to Month 12

Title

Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

Description

Time Frame

Randomization to Month 36

Title

Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36

Description

Time Frame

Randomization to Month 36

Title

Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12

Description

Time Frame

Randomization to Month 12

Title

Percent of Participants With Subclinical Rejection at Month 12

Description

Time Frame

Month 12

Title

Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36

Description

Time Frame

Randomization to Month 36

Title

Mean Value of Physical and Mental Components Using SF-36 Questionnaire

Description

Time Frame

Months 6, 12, 24, 36

Title

Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire

Description

Time Frame

Months 6, 12, 24, 36

Title

Mean Relative to an Identified Distribution (Ridit) Value of Symptom Occurrence and Symptom Distress Using Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSDS-59R)

Description

Time Frame

Months 6, 12, 24, 36

Title

Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36

Description

Time Frame

Baseline to Months 6, 12, 24,and 36

Title

Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36

Description

Time Frame

Baseline to Months 6, 12, 24, and 36

Title

Percent of Participants Surviving With a Functioning Graft

Description

Time Frame

Months 24, 36

Title

Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36

Description

Time Frame

Randomization to Month 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

University Of Alabama At Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Loma Linda University Medical Center-Transplantation Institu

City

Loma Linda

State/Province

California

ZIP/Postal Code

92354

Country

United States

Facility Name

Cedars Sinai Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Facility Name

California Institute Of Renal Research

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

University Of California San Francisco Medical Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

University Of Colorado Health Sciences Center

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Yale University School Of Medicine-Yale New Haven Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Piedmont Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30309

Country

United States

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Medical College Of Georgia

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30912

Country

United States

Facility Name

University Of Chicago Hospitals

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

University Of Iowa Hospitals And Clinics

City

Iowa City

State/Province

Indiana

ZIP/Postal Code

52242

Country

United States

Facility Name

University Of Kentucky

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536

Country

United States

Facility Name

Maine Tranplant Program

City

Portland

State/Province

Maine

ZIP/Postal Code

04102

Country

United States

Facility Name

Western New England Renal & Transplant Associates, Pc

City

Springfield

State/Province

Massachusetts

ZIP/Postal Code

01107

Country

United States

Facility Name

Henry Ford Hospital, Transplant Institute

City

Detriot

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

University Of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Washington University School Of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Recanati/Miller Transplantation Institute

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Columbia University College Of Physicians & Surgeons

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

University Of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

University Of North Carolina At Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28203

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Div Of Multi-Organ Trans, Hepato-Biliary-Pancreatic Surgery

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19102

Country

United States

Facility Name

Musc

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

27232

Country

United States

Facility Name

Baylor University Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Fletcher Allen Health Care

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05401

Country

United States

Facility Name

Inova Transplant Center

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Swedish Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

Sacred Heart Medical Ctr Providence Medical Research Ctr

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

Facility Name

University Of Wisconsin

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

Facility Name

Froedtert Memorial Lutheran Hospital

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

Facility Name

Local Institution

City

Capital Federal

State/Province

Buenos Aires

ZIP/Postal Code

C1425APQ

Country

Argentina

Facility Name

Local Institution

City

La Plata

State/Province

Buenos Aires

ZIP/Postal Code

1900

Country

Argentina

Facility Name

Local Institution

City

Cordoba, Crd

State/Province

Cordoba

ZIP/Postal Code

X5016KEH

Country

Argentina

Facility Name

Local Institution

City

Rosario

State/Province

Santa Fe

ZIP/Postal Code

2000

Country

Argentina

Facility Name

Local Institution

City

Buenos Aires

ZIP/Postal Code

C1155APP

Country

Argentina

Facility Name

Local Institution

City

Santa Fe

ZIP/Postal Code

S3000EPV

Country

Argentina

Facility Name

Local Institution

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

Local Institution

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Local Institution

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

Local Institution

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3052

Country

Australia

Facility Name

Local Institution

City

Innsbuck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Local Institution

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

Local Institution

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Local Institution

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Local Institution

City

Rio De Janeiro / Rj

State/Province

Rio De Janeiro

ZIP/Postal Code

21041

Country

Brazil

Facility Name

Local Institution

City

Porto Alegre/rs

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90035

Country

Brazil

Facility Name

Local Institution

City

Porto Alegre

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90035

Country

Brazil

Facility Name

Local Institution

City

Campinas

State/Province

Sao Paulo

ZIP/Postal Code

13033

Country

Brazil

Facility Name

Local Institution

City

Sao Paulo/sp

State/Province

Sao Paulo

ZIP/Postal Code

04038

Country

Brazil

Facility Name

Local Institution

City

Sao Paulo

ZIP/Postal Code

05403

Country

Brazil

Facility Name

Local Institution

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 2S2

Country

Canada

Facility Name

Local Institution

City

Halifax

State/Province

Nova Scotia

ZIP/Postal Code

B3H 2Y9

Country

Canada

Facility Name

Local Institution

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H1T 2M4

Country

Canada

Facility Name

Local Institution

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2L 2W5

Country

Canada

Facility Name

Local Institution

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3A 1A1

Country

Canada

Facility Name

Local Institution

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7M 0Z9

Country

Canada

Facility Name

Local Institution

City

Praha 4

ZIP/Postal Code

140 21

Country

Czech Republic

Facility Name

Local Institution

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Facility Name

Local Institution

City

Brest Cedex

ZIP/Postal Code

29609

Country

France

Facility Name

Local Institution

City

Creteil

ZIP/Postal Code

94000

Country

France

Facility Name

Local Institution

City

Grenoble Cedex 9

ZIP/Postal Code

38043

Country

France

Facility Name

Local Institution

City

Nante Cedex 01

ZIP/Postal Code

44093

Country

France

Facility Name

Local Institution

City

Paris

ZIP/Postal Code

75015

Country

France

Facility Name

Local Institution

City

Toulouse

ZIP/Postal Code

31054

Country

France

Facility Name

Local Institution

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Local Institution

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Local Institution

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Local Institution

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Local Institution

City

Szeged

ZIP/Postal Code

H-6720

Country

Hungary

Facility Name

Local Institution

City

Gujarat

State/Province

Ahmedabad

ZIP/Postal Code

380016

Country

India

Facility Name

Local Institution

City

Nadiad

State/Province

Gujarat

ZIP/Postal Code

387001

Country

India

Facility Name

Local Institution

City

Ahmedabad

State/Province

Gujrat

ZIP/Postal Code

380052

Country

India

Facility Name

Local Institution

City

Cochin

State/Province

Kerala

ZIP/Postal Code

682304

Country

India

Facility Name

Local Institution

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

400 026

Country

India

Facility Name

Local Institution

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

400016

Country

India

Facility Name

Local Institution

City

Chandigarh

ZIP/Postal Code

160012

Country

India

Facility Name

Local Institution

City

Chennai

ZIP/Postal Code

600 006

Country

India

Facility Name

Local Institution

City

Lucknow

ZIP/Postal Code

226000

Country

India

Facility Name

Local Institution

City

New Delhi

ZIP/Postal Code

110076

Country

India

Facility Name

Local Institution

City

Petah Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Local Institution

City

Milano

ZIP/Postal Code

20162

Country

Italy

Facility Name

Local Institution

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

Local Institution

City

Roma

ZIP/Postal Code

00168

Country

Italy

Facility Name

Local Institution

City

Mexico

State/Province

Distrito Federal

ZIP/Postal Code

14080

Country

Mexico

Facility Name

Local Institution

City

Cuernavaca

State/Province

Morelos

ZIP/Postal Code

62448

Country

Mexico

Facility Name

Local Institution

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Local Institution

City

Aguascalientes

ZIP/Postal Code

20000

Country

Mexico

Facility Name

Local Institution

City

Distrito Federal

ZIP/Postal Code

14080

Country

Mexico

Facility Name

Local Institution

City

San Luis Potosi

ZIP/Postal Code

78240

Country

Mexico

Facility Name

Local Institution

City

Poznan

ZIP/Postal Code

60-479

Country

Poland

Facility Name

Local Institution

City

Szczecin

ZIP/Postal Code

70-111

Country

Poland

Facility Name

Local Institution

City

Observatory

State/Province

Cape Town

ZIP/Postal Code

7925

Country

South Africa

Facility Name

Local Institution

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0002

Country

South Africa

Facility Name

Local Institution

City

Durban

State/Province

Kwa Zulu Natal

ZIP/Postal Code

4001

Country

South Africa

Facility Name

Local Institution

City

Barcelona

ZIP/Postal Code

08907

Country

Spain

Facility Name

Local Institution

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Local Institution

City

Malaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Local Institution

City

Goteborg

ZIP/Postal Code

SE-413 45

Country

Sweden

Facility Name

Local Institution

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Facility Name

Local Institution

City

Zurich

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

Local Institution

City

Antalya

ZIP/Postal Code

07059

Country

Turkey

12. IPD Sharing Statement

Citations:

PubMed Identifier

26816011

Citation

Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016 Jan 28;374(4):333-43. doi: 10.1056/NEJMoa1506027. Erratum In: N Engl J Med. 2016 Feb 18;374(7):698.

Results Reference

derived

PubMed Identifier

24831918

Citation

Dobbels F, Wong S, Min Y, Sam J, Kalsekar A. Beneficial effect of belatacept on health-related quality of life and perceived side effects: results from the BENEFIT and BENEFIT-EXT trials. Transplantation. 2014 Nov 15;98(9):960-8. doi: 10.1097/TP.0000000000000159.

Results Reference

derived

PubMed Identifier

21992533

Citation

Vincenti F, Larsen CP, Alberu J, Bresnahan B, Garcia VD, Kothari J, Lang P, Urrea EM, Massari P, Mondragon-Ramirez G, Reyes-Acevedo R, Rice K, Rostaing L, Steinberg S, Xing J, Agarwal M, Harler MB, Charpentier B. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant. 2012 Jan;12(1):210-7. doi: 10.1111/j.1600-6143.2011.03785.x. Epub 2011 Oct 12.

Results Reference

derived

Links:

URL

http://www.bms.com/studyconnect/Pages/home.aspx

Description

BMS clinical trial educational resource

Learn more about this trial

Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)

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Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT) (BENEFIT)

Kidney Transplantation, Chronic Kidney Failure

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial