Study of Belatacept in Subjects Who Are Undergoing a Renal Transplant

Renal Transplantation Clinical Trial

— BENEFIT-EXT  

Official title:

Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial - Extended Criteria Donors (BENEFIT-EXT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114777
• Other study ID #: IM103-027
• Status: Completed
• Phase: Phase 3
• First received: June 17, 2005
• Last updated: June 28, 2017
• Start date: February 2005
• Est. completion date: September 2014

Study information

• Verified date: June 2017
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to learn if Belatacept is effective and safe as a first line of immunosuppression treatment in patients undergoing a renal transplant where the donor kidney is obtained in patients with extended criteria.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 595
• Est. completion date: September 2014
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is a first-time recipient of a kidney transplant from a deceased donor.

• Specific donor criteria

Exclusion Criteria:

• Donor age <10 years

• Subjects receiving a concurrent solid organ or cell transplant (lung, heart, etc.)

• Subjects with a positive T-cell lymphocytotoxic crossmatch.

• Subjects who are positive for Hepatitis B or C, or HIV

• Active tuberculosis

• History of cancer in the last 5 years

• History of substance abuse

• Specific laboratory results are exclusionary

• Mammography suspicious for cancer

• Allergy to iodine

• For Long-term extension study-Subjects who have completed three years of study treatment (through Week 156)

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Cyclosporin A
tablet, oral, 1st month target: 150-300 ng/mL, after 1st month target: 100-250 ng/mL, daily, 36 months, 100-250 ng/mL, daily, 84 months
• Belatacept Less Intensive Regimen (LI)
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 months, 5 mg/kg every 4 weeks, q 4 weeks, 84 months
• Belatacept More Intensive Regimen (MI)
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, 5 mg/kg every 4 weeks, q 4 weeks, 84 months

Locations

Country	Name	City	State
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Cordoba, Crd	Cordoba
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Santa Fe
Australia	Local Institution	Woodville	South Australia
Austria	Local Institution	Innsbuck
Austria	Local Institution	Vienna
Belgium	Local Institution	Leuven
Brazil	Local Institution	Campinas/sp	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre/rs	Rio Grande Do Sul
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Halifax	Nova Scotia
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Saskatoon	Saskatchewan
Chile	Local Institution	Santiago	Metropolitana
Czechia	Local Institution	Prague 4
France	Local Institution	Bordeaux
France	Local Institution	Brest, Cedex 29
France	Local Institution	Creteil
France	Local Institution	Le Kremlin Bicetre Cedex
France	Local Institution	Nante Cedex 01
France	Local Institution	Paris
France	Local Institution	Toulouse Cedex
France	Local Institution	Tours Cedex 09
France	Local Institution	Vandoeuvre Les Nancy Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Erlangen
Germany	Local Institution	Essen
Germany	Local Institution	Hannover
Hungary	Local Institution	Budapest
Hungary	Local Institution	Szeged
Italy	Local Institution	Milano
Italy	Local Institution	Padova
Italy	Local Institution	Roma
Norway	Local Institution	Oslo
Poland	Local Institution	Poznan
Poland	Local Institution	Warszawa
South Africa	Local Institution	Pretoria	Gauteng
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Sweden	Local Institution	Gothenburg
United Kingdom	Local Institution	Manchester
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Transplant Institute	Atlanta	Georgia
United States	University Of Colorado Health Sciences Center	Aurora	Colorado
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Northwestern University-Feinberg School Of Medicine	Chicago	Illinois
United States	University Of Chicago Hospitals	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	Henry Ford Hospital, Transplant Institute	Detroit	Michigan
United States	National Institute Of Transplantation	Los Angeles	California
United States	Ucla Kidney & Kidney-Pancreas Transplant Research Office	Los Angeles	California
United States	University Of Wisconsin	Madison	Wisconsin
United States	Froedtert Memorial Hospital	Milwaukee	Wisconsin
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Acadiana Renal Physicians	New Iberia	Louisiana
United States	Tulane Abdominal Transplant Institute	New Orleans	Louisiana
United States	Columbia University College Of Physicians & Surgeons	New York	New York
United States	Mount Sinai School Of Medicine	New York	New York
United States	Drexel University College Of Medicine, Department Of Surgery	Philadelphia	Pennsylvania
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Sharp Memorial Hospital	San Diego	California
United States	University Of California San Francisco Medical Center	San Francisco	California
United States	Western New England Renal & Transplant Associates, Pc	Springfield	Massachusetts
United States	Lifelink Healthcare Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Hungary,  Italy,  Norway,  Poland,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Survived With a Graft at 12 Months Post-Transplant	Participant and graft survival at 12 months was summarized within each treatment group. Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine = 6.0 mg/dL (530 µmol/L) as determined by central laboratory for =4 weeks or 56 or more consecutive days of dialysis.	Month 12 post-transplant
Primary	Percentage of Participants With a Measured Glomerular Filtration Rate (GFR) <60 mL/Min Per 1.73 m^2 at Month 12 or a Decrease in Measured GFR >=10 mL/Min Per 1.73 m^2 From Month 3 to Month 12	GFR was assessed using a true measure of glomerular filtration via non-radiolabeled iothalamate clearance test using a validated procedure.	From Month 3 to Month 12
Secondary	Measured Glomerular Filtration Rate (GFR) by Month 12 and 24	GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here, 'n' signifies the number of evaluable participants for the reporting arm at the given time point. Missing measured GFR assessments were imputed to a GFR of zero.	At Month 12 and Month 24
Secondary	Percentage of Participants With Chronic Allograft Nephropathy (CAN) at Month 12	Biopsy-proven CAN was determined by a blinded central histopathologist using the Banff 97 working classification of kidney transplant pathology. Onset of CAN was determined by the biopsy date when it was observed. Participants were considered as having CAN at 12 months if: CAN observed in a biopsy either prior to 12 months (including baseline biopsy) or first post 12 months biopsy; Participant had graft loss during the first year post transplant; no biopsy available post 12 months and CAN not observed in biopsies prior to 12 months; no biopsy available either prior to or post 12 months; and the measured glomerular filtration rate from Month 3 to Month 12 decreases at least 10 mL/min/1.73m^2. All other participants with missing 12 month biopsy were considered having no CAN observed at 12 months.	At Month 12
Secondary	Percentage of Participants Who Survived With a Graft at 24 and 36 Months Post-Transplant	Participant and graft survival at 12 months was summarized within each treatment group. Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss will be defined as a sustained level of serum creatinine = 6.0 mg/dL (530 µmol/L) as determined by central laboratory for = 4 weeks or 56 or more consecutive days of dialysis.	Month 24 and Month 36 post-transplant
Secondary	Calculated Glomerular Filtration Rate (GFR) at 6, 12, 24, 36 and 84 Months	GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Months 6, 12, 24, 36 and 84
Secondary	Change in Calculated GFR at Months 12, 24, 36 and 84	GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Baseline and Months 12, 24, 36 and 84
Secondary	Number of Participants With Anti-Hypertensive Medications Used to Control Hypertension at 12, 24 and 36 Months	Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure = 130 mm Hg or standardized diastolic blood pressure = 80 mm Hg or participant had received an antihypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Baseline and Months 12, 24 and 36
Secondary	Percentage of Subjects Who Used Anti-Hypertensive Medications to Control Hypertension at Months 12, 24 and 36	Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure = 130 mm Hg or standardized diastolic blood pressure = 80 mm Hg or subject had received an anti-hypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Months 12, 24 and 36
Secondary	Percentage of Participants With New Onset Diabetes Mellitus (NODM) at 12, 24 and 36 Months.	NODM was defined as participant who did not have diabetes prior to randomization. Participants were determined for NODM if the participant received an antidiabetic medication for a duration of at least 30 days, or at least two fasting plasma glucose (FPG) tests indicate that FPG is = 126 mg/dL (7.0 mmol/L).	Months 12, 24 and 36
Secondary	Systolic and Diastolic Blood Pressure (BP) at 12, 24 and 36 Months	Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure = 130 mm Hg or standardized diastolic blood pressure = 80 mm Hg or participant had received an anti-hypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Months 12, 24 and 36
Secondary	Mean Framingham Risk Score From Baseline to Months 12, 24 and 36	The risk score was calculated based on the total points from six variables: Age, Level of LDL-cholesterol, Level of HDL-cholesterol, Presence and severity of systolic or diastolic hypertension, Presence or absence of a history of diabetes mellitus and Presence or absence of a history recent cigarette smoking. Total scores can range from <-3 to >14, which translate to a 1% to 56% risk of developing coronary heart disease in 10 years. Totals in the 4 to 6 point range translate to a 7 to 11% risk and 8 to 10 point range translate to a 18 to 27% risk.	Baseline and Months 12, 24 and 36
Secondary	Percentage of Participants Using Lipid-Lowering Therapy at 12, 24, and 36 Months	Dyslipidemia was defined as triglyceride = 500 mg/dL [5.65 mmol/L], low density lipoprotein (LDL) = 100 mg/dL [2.59 mmol/L], and non-elevated high density lipoprotein (HDL) = 130 mg/dL [3.36 mmol/L]. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Months 12, 24 and 36
Secondary	Change in Total Cholesterol (TC), Non-HDL, LDL and HDL Cholesterol and Triglycerides at 12, 24 and 36	Dyslipidemia was defined as triglyceride = 500 mg/dL [5.65 mmol/L], low density lipoprotein (LDL) = 100 mg/dL [2.59 mmol/L], and elevated non-high density lipoprotein (HDL) = 130 mg/dL [3.36 mmol/L]. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.	Months 12, 24 and 36
Secondary	Percentage of Participants Who Have an Acute Rejection by Months 6, 12, 24, 36 and 84	Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Clinically suspected acute rejection was defined as an unexplained rise of serum creatinine = 25% from baseline creatinine or an unexplained decreased urine output or fever and graft tenderness or serum creatinine that remains elevated within 14 days post--transplantation and clinical suspicion of acute rejection exists.	Months 6, 12, 24, 36 and 84
Secondary	Number of Participants Using Lymphocyte Depleting Therapy and Steroid-Resistant for Acute Rejection by Months 6, 12, 24, and 36.	Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Lymphocyte -depletion therapy for treatment of an episode of acute was defined as a participant treated with therapy and provided not treated with steroids earlier while steroid resistant acute rejection was defined as participants initially treated with steroids alone for suspected acute rejection for at least 2 days and then followed by the start of lymphocyte -depletion therapy.	Months 6, 12, 24 and 36
Secondary	Number of Participants Based on Severity of Acute Rejection Based on Banff Grade Level by Months 6, 12, 24, 36 and 84	Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Clinically suspected acute rejection was defined as an unexplained rise of serum creatinine = 25% from baseline creatinine or an unexplained decreased urine output or fever and graft tenderness or serum creatinine that remains elevated within 14 days post--transplantation and clinical suspicion of acute rejection exists.	Months 6, 12, 24, 36 and 84
Secondary	Mean Changes in Mental Component and Physical Component Health-Related Quality of Life (SF-36) From Baseline to Months 12, 24 and 36	The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline = post-baseline value - baseline value; a higher value signifies improvement.	Baseline and Months 12, 24 and 36
Secondary	Number of Participants With Clinically Significant Changes in Vital Signs up to 36 Months	Participants with abnormal blood pressure, body weight and body temperature outside the defined normal range were graded as clinically significant vital signs by the investigator.	Day 1 to Month 36
Secondary	Number of Participants With Laboratory Test Abnormalities up to 36 Months	Participants with laboratory values outside the defined normal range were graded as clinically significant laboratory abnormalities by the investigator. Subjects were analyzed for Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase(AST), Hemoglobin, Platelet Count, Leukocytes, Bilirubin, Creatinine, Calcium, Bicarbonate, Potassium, Magnesium, Sodium, Phosphorus, Albumin, Uric Acid and Protein. Laboratory abnormalities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Here 'n' signifies those subjects evaluable for this measure at specified time points for each arm, respectively.	Day 1 to Month 36
Secondary	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Related AEs and SAEs, AEs Leading to Discontinuation and Who Died up to Month 36	AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	Day 1 to Month 36
Secondary	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Related AEs and SAEs, AEs Leading to Discontinuation and Who Died up to Month 84	AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	Day 1 to Month 84
Secondary	Percentage of Participants With Graft Loss or Death to Month 84	Participant and graft survival at 84 months was summarized within each treatment group.	Randomization to date of death, up to 84 months

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