Trial record 1 of 1 for:    NCT00256750
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Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT) (BENEFIT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00256750
First received: November 15, 2005
Last updated: July 12, 2016
Last verified: July 2016
Results First Received: May 24, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Subject);   Primary Purpose: Treatment
Conditions: Kidney Transplantation
Chronic Kidney Failure
Interventions: Drug: Cyclosporine (CsA)
Drug: Belatacept LI (less intensive)
Drug: Belatacept MI (more intensive)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
738 participants enrolled, 686 randomized. Reasons for non-randomization include 5 participants withdrew consent, 1 lost to follow-up, 34 no longer met study criteria, and 12 for other non-listed reasons. 666 participants randomized, but not transplanted. 20 not transplanted; 10, 4, 6 in the CsA, Belatacept LI, Belatacept MI, respectively.

Reporting Groups
  Description
Cyclosporine

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI 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 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Participant Flow for 5 periods

Period 1:   Transplanted Pre-Treatment
    Cyclosporine     Belatacept LI     Belatacept MI  
STARTED     221     226     219  
COMPLETED     215     226     219  
NOT COMPLETED     6     0     0  
Withdrawal by Subject                 3                 0                 0  
Not Specified                 2                 0                 0  
Death                 1                 0                 0  

Period 2:   Post-Transplant Treated (12 Months)
    Cyclosporine     Belatacept LI     Belatacept MI  
STARTED     215     226     219  
COMPLETED     174     183     173  
NOT COMPLETED     41     43     46  
Adverse Event                 20                 12                 8  
Death                 3                 2                 4  
Lack of Efficacy                 10                 22                 27  
Lost to Follow-up                 1                 0                 0  
Not Specified                 5                 4                 2  
Withdrawal by Subject                 0                 3                 5  
Protocol Violation                 2                 0                 0  

Period 3:   Post-Transplant Treated (24 Months)
    Cyclosporine     Belatacept LI     Belatacept MI  
STARTED     174     183     173  
COMPLETED     153     176     164  
NOT COMPLETED     21     7     9  
Adverse Event                 7                 3                 6  
Withdrawal by Subject                 5                 1                 0  
Death                 3                 0                 0  
Lack of Efficacy                 4                 3                 2  
Not Specified                 2                 0                 1  

Period 4:   Post-Transplant Treated (36 Months)
    Cyclosporine     Belatacept LI     Belatacept MI  
STARTED     153     176     164  
COMPLETED     143     170     158  
NOT COMPLETED     10     6     6  
Adverse Event                 5                 1                 2  
Withdrawal by Subject                 1                 0                 1  
Death                 0                 2                 1  
Subject no longer meets study criteria                 0                 0                 1  
Lack of Efficacy                 4                 1                 0  
Protocol Violation                 0                 1                 0  
Not specified                 0                 1                 1  

Period 5:   Long Term Extension (LTE; 84 Months)
    Cyclosporine     Belatacept LI     Belatacept MI  
STARTED     136 [1]   166 [2]   155 [3]
COMPLETED     89     136     127  
NOT COMPLETED     47     30     28  
Adverse Event                 13                 11                 14  
Withdrawal by Subject                 5                 4                 1  
Lost to Follow-up                 4                 1                 1  
Death                 9                 4                 4  
Lack of Efficacy                 6                 3                 0  
Poor/Non-compliance                 4                 1                 1  
Pregnancy                 0                 1                 2  
Administrative Reason By Sponsor                 1                 1                 0  
Not Specified                 5                 4                 5  
[1] Participants on drug through month 36 eligible to enroll in LTE; 2 ineligible, 5 withdrew or refused
[2] Participants on drug through month 36 were eligible to enroll in LTE; 4 withdrew or refused.
[3] Participants on drug through month 36 were eligible to enroll in LTE; 3 withdrew or refused.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline characteristics of transplant recipients: All randomized and transplanted participants, intent to treat (ITT) population

Reporting Groups
  Description
Cyclosporine

Cyclosporine (CsA): tablet, oral

1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Belatacept LI Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)
Belatacept MI 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)
Total Total of all reporting groups

Baseline Measures
    Cyclosporine     Belatacept LI     Belatacept MI     Total  
Number of Participants  
[units: participants]
  221     226     219     666  
Age  
[units: years]
Mean (Standard Deviation)
  43.5  (14.3)     42.6  (13.4)     43.6  (14.6)     43.2  (14.1)  
Age, Customized  
[units: participants]
       
Between 18 and 45 years:     110     124     111     345  
Between 46 and 65 years:     101     93     93     287  
> 65 years:     10     9     15     34  
Gender  
[units: participants]
       
Female     56     80     68     204  
Male     165     146     151     462  
Previous Number of Transplant  
[units: participants]
       
0     208     218     210     636  
1     9     5     5     19  
2     0     0     1     1  
Missing     4     3     3     10  



  Outcome Measures
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1.  Primary:   Percent of Participants Surviving With a Functioning Graft by Month 12   [ Time Frame: Day 1 to Month 12 ]

2.  Primary:   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   [ Time Frame: Month 12; Month 3 to Month 12 ]

3.  Primary:   Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12   [ Time Frame: Day 1 to Month 12 ]

4.  Secondary:   Mean Value of the Measured Glomerular Filtration Rate (mGFR)   [ Time Frame: Months 3, 12, 24 ]

5.  Secondary:   Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12   [ Time Frame: Month 12 ]

6.  Secondary:   Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84   [ Time Frame: Randomization to Month 84 ]

7.  Secondary:   Number of Participants With Adverse Events of Special Interest by Month 84   [ Time Frame: Randomization to Month 84 ]

8.  Secondary:   Mean Blood Pressure at Month 84   [ Time Frame: Month 84 ]

9.  Secondary:   Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36   [ Time Frame: Baseline to Month 36 ]

10.  Secondary:   Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84   [ Time Frame: Randomization to Month 84 ]

11.  Secondary:   Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24   [ Time Frame: Month 3 to Month 12; Month 3 to Month 24 ]

12.  Secondary:   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   [ Time Frame: Month 3 to Month 12 ]

13.  Secondary:   Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12   [ Time Frame: Month 12 ]

14.  Secondary:   Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation   [ Time Frame: Months 6, 12, 24, 36 ]

15.  Secondary:   Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12   [ Time Frame: Month 6 to Month 12 ]

16.  Secondary:   Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36   [ Time Frame: Week 4 post-transplantation to Month 36 ]

17.  Secondary:   Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36   [ Time Frame: Month 36 ]

18.  Secondary:   Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12   [ Time Frame: Month 12 ]

19.  Secondary:   Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12   [ Time Frame: Month 12 ]

20.  Secondary:   Mean Systolic Blood Pressure and Diastolic Blood Pressure   [ Time Frame: Months 12, 24, 36 ]

21.  Secondary:   Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12   [ Time Frame: Day 1 to Month 12 ]

22.  Secondary:   Percent of Participants With Prevalence of Controlled Hypertension at Month 12   [ Time Frame: Month 12 ]

23.  Secondary:   Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12   [ Time Frame: Randomization to Month 12 ]

24.  Secondary:   Percent of Participants With Prevalence of Dyslipidemia at Month 12   [ Time Frame: Month 12 ]

25.  Secondary:   Percent of Participants With Controlled Dyslipidemia at Month 12   [ Time Frame: Month 12 ]

26.  Secondary:   Number of Participants With Antihyperlipidemic Medication by Intensity Level   [ Time Frame: Month 36 ]

27.  Secondary:   Percent of Participants Using At Least One Anti-Hyperlipidemic Medication   [ Time Frame: Month 36 ]

28.  Secondary:   Mean Value of Lipid Parameters   [ Time Frame: Months 12, 24, 36 ]

29.  Secondary:   Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36   [ Time Frame: Randomization to Month 36 ]

30.  Secondary:   Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36   [ Time Frame: Randomization to Month 36 ]

31.  Secondary:   Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12   [ Time Frame: Randomization to Month 12 ]

32.  Secondary:   Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36   [ Time Frame: Randomization to Month 36 ]

33.  Secondary:   Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36   [ Time Frame: Randomization to Month 36 ]

34.  Secondary:   Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12   [ Time Frame: Randomization to Month 12 ]

35.  Secondary:   Percent of Participants With Subclinical Rejection at Month 12   [ Time Frame: Month 12 ]

36.  Secondary:   Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36   [ Time Frame: Randomization to Month 36 ]

37.  Secondary:   Mean Value of Physical and Mental Components Using SF-36 Questionnaire   [ Time Frame: Months 6, 12, 24, 36 ]

38.  Secondary:   Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire   [ Time Frame: Months 6, 12, 24, 36 ]

39.  Secondary:   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)   [ Time Frame: Months 6, 12, 24, 36 ]

40.  Secondary:   Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36   [ Time Frame: Baseline to Months 6, 12, 24,and 36 ]

41.  Secondary:   Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36   [ Time Frame: Baseline to Months 6, 12, 24, and 36 ]

42.  Secondary:   Percent of Participants Surviving With a Functioning Graft   [ Time Frame: Months 24, 36 ]

43.  Secondary:   Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36   [ Time Frame: Randomization to Month 36 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00256750     History of Changes
Obsolete Identifiers: NCT00432497
Other Study ID Numbers: IM103-008
Study First Received: November 15, 2005
Results First Received: May 24, 2016
Last Updated: July 12, 2016
Health Authority: United States: Food and Drug Administration