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Belatacept Post Depletional Repopulation to Facilitate Tolerance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00565773
Recruitment Status : Completed
First Posted : November 30, 2007
Results First Posted : January 30, 2020
Last Update Posted : February 11, 2020
Sponsor:
Collaborators:
Bristol-Myers Squibb
Duke University
Information provided by (Responsible Party):
Allan D Kirk, MD, PhD, Emory University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Organ Transplantation
Interventions Drug: Belatacept
Drug: Sirolimus
Drug: Alemtuzumab
Enrollment 40
Recruitment Details Enrollment began in December 2007 and all study activities completed on July 1, 2017 Participants were enrolled from patients of Emory University Hospital and the Emory Clinic in Atlanta, Georgia.
Pre-assignment Details  
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Period Title: Overall Study
Started 40
Completed 38
Not Completed 2
Reason Not Completed
Withdrawal by Subject             1
Physician Decision             1
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 40 participants
46.5
(20 to 69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
13
  32.5%
Male
27
  67.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
15
  37.5%
White
24
  60.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
 100.0%
Also received a bone marrow transfusion  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
9
  22.5%
Type of Transplant  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Living donor transplant
30
  75.0%
Deceased donor transplant
10
  25.0%
Body Mass Index (BMI)  
Median (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 40 participants
26.0
(18.6 to 37.3)
1.Primary Outcome
Title Number of Patients Successfully Withdrawn From Oral Immunosuppression
Hide Description The primary endpoint is the number of patients successfully withdrawn from oral immunosuppression (sirolimus) for one year after their last dose of sirolimus. After taking sirolimus for one year, participants meeting certain pre-specified criteria were offered the opportunity to wean from sirolimus and continue with belatacept monotherapy. To be eligible for weaning of sirolimus, participants were required to have a kidney biopsy negative for all signs of rejection, including borderline findings.
Time Frame Year 2
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis includes participants meeting criteria to wean from sirolimus who also opted to attempt sirolimus weaning.
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
Successful weaning
12
  63.2%
Failed weaning
7
  36.8%
2.Secondary Outcome
Title Number of Participants Experiencing Costimulation Blockade-resistant Rejection (CoBRR)
Hide Description Assessment of the proposed therapies to prevent biopsy proven acute rejection, also known as CoBRR, was determined by the number of participants experiencing CoBRR at 1, 3 and 5 years post-transplant.
Time Frame Year 1, Year 3, Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Year 1 Number Analyzed 40 participants
0
   0.0%
Year 3 Number Analyzed 40 participants
0
   0.0%
Year 5 Number Analyzed 38 participants
0
   0.0%
3.Secondary Outcome
Title Number of Participants Experiencing Chronic Allograft Nephropathy (CAN)
Hide Description Assessment of biopsy proven chronic allograft nephropathy at 1, 3 and 5 years post-transplant is presented as the number of participants experiencing CAN.
Time Frame Year 1, Year 3, Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Year 1 Number Analyzed 40 participants
0
   0.0%
Year 3 Number Analyzed 40 participants
0
   0.0%
Year 5 Number Analyzed 38 participants
0
   0.0%
4.Secondary Outcome
Title Number of Participants With BK Viremia
Hide Description The number of participants experiencing BK viremia, an opportunistic infection, during the study is presented here.
Time Frame Up to Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
17
  42.5%
5.Secondary Outcome
Title Number of Participants Developing Donor-specific Alloantibody (DSA)
Hide Description Long term assessment of donor-specific immune responsiveness after prolonged therapy with belatacept (with or without sirolimus), and during and following drug withdrawal as determined by in vitro alloresponsiveness in carboxyfluorescein succinimidyl ester (CFSE) mixed lymphocyte reactivity and intracellular cytokine staining (ICCS).
Time Frame Up to Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
5
  12.5%
6.Secondary Outcome
Title Number of Participants With Surviving Grafts
Hide Description The number of participants whose grafts survived without graft failure at each follow up time point is presented here.
Time Frame Year 1, Year 3, Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Year 1 Number Analyzed 40 participants
40
 100.0%
Year 3 Number Analyzed 40 participants
40
 100.0%
Year 5 Number Analyzed 38 participants
36
  94.7%
7.Secondary Outcome
Title Estimated Glomerular Filtration Rate (eGFR)
Hide Description Graft function was assessed throughout the study by the estimated glomerular filtration rate. The eGFR indicates the percentage of kidney function that a person has based on creatinine, age, body size, and gender. An eGFR of below 60 indicates chronic kidney disease. A higher eGFR means that there is greater kidney function.
Time Frame Year 1, Year 3, Year 5
Hide Outcome Measure Data
Hide Analysis Population Description
Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description:
Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Year 1 Number Analyzed 40 participants
70  (23)
Year 3 Number Analyzed 40 participants
67  (21)
Year 5 Number Analyzed 38 participants
71  (19)
Time Frame Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
Adverse Event Reporting Description Only adverse events that were related to the study medications (Alemtuzumab, Sirolimus, Belatacept) were recorded during the course of this study. Certain adverse events that occur commonly in this study population were not recorded as an adverse event, unless it was believed to be associated with the study medications or met the definition of a serious adverse event. Pre-existing conditions were not considered adverse events.
 
Arm/Group Title Immunosuppresive Medication Combination
Hide Arm/Group Description Renal transplant recipients receiving an experimental combination of immunosuppressive medications. Participants received a single dose of alemtuzumab on the day of transplantation and receive belatacept and sirolimus for one year.
All-Cause Mortality
Immunosuppresive Medication Combination
Affected / at Risk (%)
Total   0/40 (0.00%) 
Hide Serious Adverse Events
Immunosuppresive Medication Combination
Affected / at Risk (%)
Total   0/40 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Immunosuppresive Medication Combination
Affected / at Risk (%)
Total   14/40 (35.00%) 
Cardiac disorders   
Pericardial effusion *  1/40 (2.50%) 
General disorders   
Edema *  3/40 (7.50%) 
Musculoskeletal and connective tissue disorders   
Arthralgia *  2/40 (5.00%) 
Skin and subcutaneous tissue disorders   
Shingles *  2/40 (5.00%) 
HHV-8/Kaposi's sarcoma *  1/40 (2.50%) 
Mouth ulcers (sirolimus-associated) *  9/40 (22.50%) 
Surgical and medical procedures   
Incisional hernia *  2/40 (5.00%) 
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Allan D. Kirk, MD, PhD
Organization: Duke University
Phone: 919-681-1400
EMail: allan.kirk@duke.edu
Publications of Results:
Xu H, Bendersky VA, Brennan TV, Espinosa JR, Kirk AD. IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection. Am J Transplant. 2018 Mar;18(3):720-730. doi: 10.1111/ajt.14589. Epub 2017 Dec 12.
Xu H, Samy KP, Guasch A, Mead SI, Ghali A, Mehta A, Stempora L, Kirk AD. Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients. Am J Transplant. 2016 Feb;16(2):550-64. doi: 10.1111/ajt.13469. Epub 2015 Oct 5.
Kirk AD, Guasch A, Xu H, Cheeseman J, Mead SI, Ghali A, Mehta AK, Wu D, Gebel H, Bray R, Horan J, Kean LS, Larsen CP, Pearson TC. Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors. Am J Transplant. 2014 May;14(5):1142-51. doi: 10.1111/ajt.12712. Epub 2014 Mar 31.
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Allan D Kirk, MD, PhD, Emory University
ClinicalTrials.gov Identifier: NCT00565773    
Other Study ID Numbers: IRB00005064
Grant # FD-R-003539 ( Other Grant/Funding Number: FDA Office of Orphan Products )
BMS IM103-036 ( Other Identifier: Other )
First Submitted: November 28, 2007
First Posted: November 30, 2007
Results First Submitted: January 21, 2020
Results First Posted: January 30, 2020
Last Update Posted: February 11, 2020