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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00114777




Registration number
NCT00114777
Ethics application status
Date submitted
17/06/2005
Date registered
20/06/2005
Date last updated
7/07/2017

Titles & IDs
Public title
Study of Belatacept in Subjects Who Are Undergoing a Renal Transplant
Scientific title
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial - Extended Criteria Donors (BENEFIT-EXT)
Secondary ID [1] 0 0
IM103-027
Universal Trial Number (UTN)
Trial acronym
BENEFIT-EXT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Transplantation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclosporin A
Treatment: Drugs - Belatacept Less Intensive Regimen (LI)
Treatment: Drugs - Belatacept More Intensive Regimen (MI)

Active Comparator: Cyclosporin A -

Experimental: Belatacept Less Intensive Regimen (LI) -

Experimental: Belatacept More Intensive Regimen (MI) -


Treatment: Drugs: 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

Treatment: Drugs: 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

Treatment: Drugs: 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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Month 12 post-transplant
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
From Month 3 to Month 12
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
At Month 12 and Month 24
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
At Month 12
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Month 24 and Month 36 post-transplant
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Months 6, 12, 24, 36 and 84
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline and Months 12, 24, 36 and 84
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline and Months 12, 24 and 36
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Months 12, 24 and 36
Secondary outcome [8] 0 0
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).
Timepoint [8] 0 0
Months 12, 24 and 36
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Months 12, 24 and 36
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline and Months 12, 24 and 36
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Months 12, 24 and 36
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Months 12, 24 and 36
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Months 6, 12, 24, 36 and 84
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Months 6, 12, 24 and 36
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Months 6, 12, 24, 36 and 84
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Baseline and Months 12, 24 and 36
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
Day 1 to Month 36
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Day 1 to Month 36
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Day 1 to Month 36
Secondary outcome [20] 0 0
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.
Timepoint [20] 0 0
Day 1 to Month 84
Secondary outcome [21] 0 0
Percentage of Participants With Graft Loss or Death to Month 84 - Participant and graft survival at 84 months was summarized within each treatment group.
Timepoint [21] 0 0
Randomization to date of death, up to 84 months

Eligibility
Key inclusion criteria
- Subject is a first-time recipient of a kidney transplant from a deceased donor.

- Specific donor criteria
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Local Institution - Woodville
Recruitment postcode(s) [1] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
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State/province [11] 0 0
Minnesota
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United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
Argentina
State/province [18] 0 0
Buenos Aires
Country [19] 0 0
Argentina
State/province [19] 0 0
Cordoba
Country [20] 0 0
Argentina
State/province [20] 0 0
Santa Fe
Country [21] 0 0
Austria
State/province [21] 0 0
Innsbuck
Country [22] 0 0
Austria
State/province [22] 0 0
Vienna
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio Grande Do Sul
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio De Janeiro
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Nova Scotia
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Canada
State/province [30] 0 0
Saskatchewan
Country [31] 0 0
Chile
State/province [31] 0 0
Metropolitana
Country [32] 0 0
Czechia
State/province [32] 0 0
Prague 4
Country [33] 0 0
France
State/province [33] 0 0
Bordeaux
Country [34] 0 0
France
State/province [34] 0 0
Brest, Cedex 29
Country [35] 0 0
France
State/province [35] 0 0
Creteil
Country [36] 0 0
France
State/province [36] 0 0
Le Kremlin Bicetre Cedex
Country [37] 0 0
France
State/province [37] 0 0
Nante Cedex 01
Country [38] 0 0
France
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Paris
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France
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Toulouse Cedex
Country [40] 0 0
France
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Tours Cedex 09
Country [41] 0 0
France
State/province [41] 0 0
Vandoeuvre Les Nancy Cedex
Country [42] 0 0
Germany
State/province [42] 0 0
Berlin
Country [43] 0 0
Germany
State/province [43] 0 0
Erlangen
Country [44] 0 0
Germany
State/province [44] 0 0
Essen
Country [45] 0 0
Germany
State/province [45] 0 0
Hannover
Country [46] 0 0
Hungary
State/province [46] 0 0
Budapest
Country [47] 0 0
Hungary
State/province [47] 0 0
Szeged
Country [48] 0 0
Italy
State/province [48] 0 0
Milano
Country [49] 0 0
Italy
State/province [49] 0 0
Padova
Country [50] 0 0
Italy
State/province [50] 0 0
Roma
Country [51] 0 0
Norway
State/province [51] 0 0
Oslo
Country [52] 0 0
Poland
State/province [52] 0 0
Poznan
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
South Africa
State/province [54] 0 0
Gauteng
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Madrid
Country [57] 0 0
Spain
State/province [57] 0 0
Malaga
Country [58] 0 0
Sweden
State/province [58] 0 0
Gothenburg
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00114777
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications