Clinical trial NCT00256750: Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)
Official title: Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Transplantation
Chronic Kidney Failure
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-11-22
Enrollment: 738
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Percent of Participants Surviving With a Functioning Graft by Month 12
timeFrame: Day 1 to Month 12
measure: 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
timeFrame: Month 12; Month 3 to Month 12
measure: Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12
timeFrame: Day 1 to Month 12
Secondary outcomes:
measure: Mean Value of the Measured Glomerular Filtration Rate (mGFR)
timeFrame: Months 3, 12, 24
measure: Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12
timeFrame: Month 12
measure: Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84
timeFrame: Randomization to Month 84
measure: Number of Participants With Adverse Events of Special Interest by Month 84
timeFrame: Randomization to Month 84
measure: Mean Blood Pressure at Month 84
timeFrame: Month 84
measure: Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36
timeFrame: Baseline to Month 36
measure: Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84
timeFrame: Randomization to Month 84
measure: Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24
timeFrame: Month 3 to Month 12; Month 3 to Month 24
measure: 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
timeFrame: Month 3 to Month 12
measure: Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12
timeFrame: Month 12
measure: Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation
timeFrame: Months 6, 12, 24, 36
measure: Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12
timeFrame: Month 6 to Month 12
measure: Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36
timeFrame: Week 4 post-transplantation to Month 36
measure: Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36
timeFrame: Month 36
measure: Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12
timeFrame: Month 12
measure: Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12
timeFrame: Month 12
measure: Mean Systolic Blood Pressure and Diastolic Blood Pressure
timeFrame: Months 12, 24, 36
measure: Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12
timeFrame: Day 1 to Month 12
measure: Percent of Participants With Prevalence of Controlled Hypertension at Month 12
timeFrame: Month 12
measure: Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12
timeFrame: Randomization to Month 12
measure: Percent of Participants With Prevalence of Dyslipidemia at Month 12
timeFrame: Month 12
measure: Percent of Participants With Controlled Dyslipidemia at Month 12
timeFrame: Month 12
measure: Number of Participants With Antihyperlipidemic Medication by Intensity Level
timeFrame: Month 36
measure: Percent of Participants Using At Least One Anti-Hyperlipidemic Medication
timeFrame: Month 36
measure: Mean Value of Lipid Parameters
timeFrame: Months 12, 24, 36
measure: Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36
timeFrame: Randomization to Month 36
measure: Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36
timeFrame: Randomization to Month 36
measure: Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12
timeFrame: Randomization to Month 12
measure: Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36
timeFrame: Randomization to Month 36
measure: Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36
timeFrame: Randomization to Month 36
measure: Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12
timeFrame: Randomization to Month 12
measure: Percent of Participants With Subclinical Rejection at Month 12
timeFrame: Month 12
measure: Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36
timeFrame: Randomization to Month 36
measure: Mean Value of Physical and Mental Components Using SF-36 Questionnaire
timeFrame: Months 6, 12, 24, 36
measure: Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire
timeFrame: Months 6, 12, 24, 36
measure: 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)
timeFrame: Months 6, 12, 24, 36
measure: Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36
timeFrame: Baseline to Months 6, 12, 24,and 36
measure: Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36
timeFrame: Baseline to Months 6, 12, 24, and 36
measure: Percent of Participants Surviving With a Functioning Graft
timeFrame: Months 24, 36
measure: Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36
timeFrame: Randomization to Month 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center-Transplantation Institu
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Diego
country: United States
facility: California Institute Of Renal Research
state: California
city: San Francisco
country: United States
facility: University Of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado Health Sciences Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine-Yale New Haven Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Medical College Of Georgia
state: Georgia
city: Chicago
country: United States
facility: University Of Chicago Hospitals
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa Hospitals And Clinics
state: Indiana
city: Lexington
country: United States
facility: University Of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Tranplant Program
state: Maine
city: Springfield
country: United States
facility: Western New England Renal & Transplant Associates, Pc
state: Massachusetts
city: Detriot
country: United States
facility: Henry Ford Hospital, Transplant Institute
state: Michigan
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Recanati/Miller Transplantation Institute
state: New York
city: New York
country: United States
facility: Columbia University College Of Physicians & Surgeons
state: New York
city: Rochester
country: United States
facility: University Of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Div Of Multi-Organ Trans, Hepato-Biliary-Pancreatic Surgery
state: Pennsylvania
city: Charleston
country: United States
facility: Musc
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Fairfax
country: United States
facility: Inova Transplant Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Spokane
country: United States
facility: Sacred Heart Medical Ctr Providence Medical Research Ctr
state: Washington
city: Madison
country: United States
facility: University Of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: La Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Cordoba, Crd
country: Argentina
facility: Local Institution
state: Cordoba
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Santa Fe
country: Argentina
facility: Local Institution
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution
state: New South Wales
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Innsbuck
country: Austria
facility: Local Institution
city: Vienna
country: Austria
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Rio De Janeiro / Rj
country: Brazil
facility: Local Institution
state: Rio De Janeiro
city: Porto Alegre/rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo/sp
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Halifax
country: Canada
facility: Local Institution
state: Nova Scotia
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Praha 4
country: Czech Republic
facility: Local Institution
city: Bordeaux
country: France
facility: Local Institution
city: Brest Cedex
country: France
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Grenoble Cedex 9
country: France
facility: Local Institution
city: Nante Cedex 01
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Szeged
country: Hungary
facility: Local Institution
city: Gujarat
country: India
facility: Local Institution
state: Ahmedabad
city: Nadiad
country: India
facility: Local Institution
state: Gujarat
city: Ahmedabad
country: India
facility: Local Institution
state: Gujrat
city: Cochin
country: India
facility: Local Institution
state: Kerala
city: Mumbai
country: India
facility: Local Institution
state: Maharashtra
city: Mumbai
country: India
facility: Local Institution
state: Maharashtra
city: Chandigarh
country: India
facility: Local Institution
city: Chennai
country: India
facility: Local Institution
city: Lucknow
country: India
facility: Local Institution
city: New Delhi
country: India
facility: Local Institution
city: Petah Tikva
country: Israel
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Cuernavaca
country: Mexico
facility: Local Institution
state: Morelos
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Distrito Federal
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Szczecin
country: Poland
facility: Local Institution
city: Observatory
country: South Africa
facility: Local Institution
state: Cape Town
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Durban
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution
city: Goteborg
country: Sweden
facility: Local Institution
city: Bern
country: Switzerland
facility: Local Institution
city: Zurich
country: Switzerland
facility: Local Institution
city: Antalya
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.
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.
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.