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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00256750




Registration number
NCT00256750
Ethics application status
Date submitted
15/11/2005
Date registered
22/11/2005
Date last updated
19/08/2016

Titles & IDs
Public title
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)
Scientific title
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)
Secondary ID [1] 0 0
IM103-008
Universal Trial Number (UTN)
Trial acronym
BENEFIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplantation 0 0
Chronic Kidney Failure 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclosporine (CsA)
Treatment: Drugs - Belatacept LI (less intensive)
Treatment: Drugs - Belatacept MI (more intensive)

Active comparator: Cyclosporine (CsA) -

Experimental: Belatacept LI (less intensive) -

Experimental: Belatacept MI (more intensive) -


Treatment: Drugs: Cyclosporine (CsA)
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)

Treatment: Drugs: Belatacept LI (less intensive)
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)

Treatment: Drugs: Belatacept MI (more intensive)
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent of Participants Surviving With a Functioning Graft by Month 12
Timepoint [1] 0 0
Day 1 to Month 12
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Month 12; Month 3 to Month 12
Primary outcome [3] 0 0
Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12
Timepoint [3] 0 0
Day 1 to Month 12
Secondary outcome [1] 0 0
Mean Value of the Measured Glomerular Filtration Rate (mGFR)
Timepoint [1] 0 0
Months 3, 12, 24
Secondary outcome [2] 0 0
Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12
Timepoint [2] 0 0
Month 12
Secondary outcome [3] 0 0
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84
Timepoint [3] 0 0
Randomization to Month 84
Secondary outcome [4] 0 0
Number of Participants With Adverse Events of Special Interest by Month 84
Timepoint [4] 0 0
Randomization to Month 84
Secondary outcome [5] 0 0
Mean Blood Pressure at Month 84
Timepoint [5] 0 0
Month 84
Secondary outcome [6] 0 0
Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36
Timepoint [6] 0 0
Baseline to Month 36
Secondary outcome [7] 0 0
Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84
Timepoint [7] 0 0
Randomization to Month 84
Secondary outcome [8] 0 0
Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24
Timepoint [8] 0 0
Month 3 to Month 12; Month 3 to Month 24
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Month 3 to Month 12
Secondary outcome [10] 0 0
Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12
Timepoint [10] 0 0
Month 12
Secondary outcome [11] 0 0
Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation
Timepoint [11] 0 0
Months 6, 12, 24, 36
Secondary outcome [12] 0 0
Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12
Timepoint [12] 0 0
Month 6 to Month 12
Secondary outcome [13] 0 0
Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36
Timepoint [13] 0 0
Week 4 post-transplantation to Month 36
Secondary outcome [14] 0 0
Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36
Timepoint [14] 0 0
Month 36
Secondary outcome [15] 0 0
Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12
Timepoint [15] 0 0
Month 12
Secondary outcome [16] 0 0
Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12
Timepoint [16] 0 0
Month 12
Secondary outcome [17] 0 0
Mean Systolic Blood Pressure and Diastolic Blood Pressure
Timepoint [17] 0 0
Months 12, 24, 36
Secondary outcome [18] 0 0
Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12
Timepoint [18] 0 0
Day 1 to Month 12
Secondary outcome [19] 0 0
Percent of Participants With Prevalence of Controlled Hypertension at Month 12
Timepoint [19] 0 0
Month 12
Secondary outcome [20] 0 0
Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12
Timepoint [20] 0 0
Randomization to Month 12
Secondary outcome [21] 0 0
Percent of Participants With Prevalence of Dyslipidemia at Month 12
Timepoint [21] 0 0
Month 12
Secondary outcome [22] 0 0
Percent of Participants With Controlled Dyslipidemia at Month 12
Timepoint [22] 0 0
Month 12
Secondary outcome [23] 0 0
Number of Participants With Antihyperlipidemic Medication by Intensity Level
Timepoint [23] 0 0
Month 36
Secondary outcome [24] 0 0
Percent of Participants Using At Least One Anti-Hyperlipidemic Medication
Timepoint [24] 0 0
Month 36
Secondary outcome [25] 0 0
Mean Value of Lipid Parameters
Timepoint [25] 0 0
Months 12, 24, 36
Secondary outcome [26] 0 0
Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36
Timepoint [26] 0 0
Randomization to Month 36
Secondary outcome [27] 0 0
Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36
Timepoint [27] 0 0
Randomization to Month 36
Secondary outcome [28] 0 0
Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12
Timepoint [28] 0 0
Randomization to Month 12
Secondary outcome [29] 0 0
Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36
Timepoint [29] 0 0
Randomization to Month 36
Secondary outcome [30] 0 0
Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36
Timepoint [30] 0 0
Randomization to Month 36
Secondary outcome [31] 0 0
Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12
Timepoint [31] 0 0
Randomization to Month 12
Secondary outcome [32] 0 0
Percent of Participants With Subclinical Rejection at Month 12
Timepoint [32] 0 0
Month 12
Secondary outcome [33] 0 0
Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36
Timepoint [33] 0 0
Randomization to Month 36
Secondary outcome [34] 0 0
Mean Value of Physical and Mental Components Using SF-36 Questionnaire
Timepoint [34] 0 0
Months 6, 12, 24, 36
Secondary outcome [35] 0 0
Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire
Timepoint [35] 0 0
Months 6, 12, 24, 36
Secondary outcome [36] 0 0
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)
Timepoint [36] 0 0
Months 6, 12, 24, 36
Secondary outcome [37] 0 0
Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36
Timepoint [37] 0 0
Baseline to Months 6, 12, 24,and 36
Secondary outcome [38] 0 0
Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36
Timepoint [38] 0 0
Baseline to Months 6, 12, 24, and 36
Secondary outcome [39] 0 0
Percent of Participants Surviving With a Functioning Graft
Timepoint [39] 0 0
Months 24, 36
Secondary outcome [40] 0 0
Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36
Timepoint [40] 0 0
Randomization to Month 36

Eligibility
Key inclusion criteria
* The subject is a recipient of a living donor or deceased donor kidney transplant.
* Male or Female, 18 or older
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

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
1/03/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2015
Sample size
Target
Accrual to date
Final
738
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment hospital [2] 0 0
Local Institution - Westmead
Recruitment hospital [3] 0 0
Local Institution - Adelaide
Recruitment hospital [4] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3052 - Parkville
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
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
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United States of America
State/province [8] 0 0
Kentucky
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United States of America
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Maine
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New York
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North Carolina
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Vermont
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Washington
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Wisconsin
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Argentina
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Argentina
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Cordoba
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Argentina
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Santa Fe
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Innsbuck
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Vienna
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Gent
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Leuven
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Rio De Janeiro
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Brazil
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Rio Grande Do Sul
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Sao Paulo
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India
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Lucknow
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India
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New Delhi
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Israel
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Italy
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Milano
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Padova
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Roma
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Mexico
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Distrito Federal
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Mexico
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Morelos
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Nuevo Leon
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Mexico
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Aguascalientes
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Mexico
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San Luis Potosi
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Poland
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Poznan
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Poland
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Szczecin
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South Africa
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Cape Town
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South Africa
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Gauteng
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South Africa
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Kwa Zulu Natal
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Sweden
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Goteborg
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Switzerland
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Bern
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Switzerland
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Zurich
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Turkey
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Antalya

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 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.
Trial website
https://clinicaltrials.gov/study/NCT00256750
Trial related presentations / publications
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. doi: 10.1056/NEJMx160003.
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.
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.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00256750