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Islet Transplantation Using Abatacept

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ClinicalTrials.gov Identifier: NCT00276250
Recruitment Status : Completed
First Posted : January 13, 2006
Results First Posted : July 27, 2016
Last Update Posted : July 27, 2016
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Nicole Turgeon MD, Emory University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Efalizumab
Drug: Abatacept
Drug: Belatacept
Enrollment 5
Recruitment Details  
Pre-assignment Details Nine subjects signed informed consent. During evaluation, four participants were found ineligible for study inclusion. Five participants completed the evaluation process and were listed for an islet transplant
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Period Title: Overall Study
Started 4 1 0
Completed 4 1 0
Not Completed 0 0 0
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen Total
Hide Arm/Group Description Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation. Total of all reporting groups
Overall Number of Baseline Participants 4 1 0 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 4 participants 1 participants 0 participants 5 participants
<=18 years 0 0 0
Between 18 and 65 years 4 1 5
>=65 years 0 0 0
Gender  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 4 participants 1 participants 0 participants 5 participants
Female 1 1 2
Male 3 0 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 1 participants 0 participants 5 participants
4 1 5
1.Primary Outcome
Title The Number of Insulin-independent Subjects at Day 75 (± 5 Days) Following the First Islet Cell Transplantation
Hide Description [Not Specified]
Time Frame 75 days post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
4 1
2.Secondary Outcome
Title Number of Insulin-independent Subjects Following Islet Transplantation
Hide Description Participants who did not need to take insulin at 1, 3, 6, 9, 12, 18, and 24 months following islet transplantation
Time Frame 1, 3, 6, 9,12,18 and 24 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
1 Month Post-Transplant 4 0
3 Months Post-Transplant 4 0
6 Months Post-Transplant 4 0
9 Months Post-Transplant 3 0
12 Months Post-Transplant 3 0
18 Months Post-Transplant 2 0
24 Months Post-Transplant 2 0
3.Secondary Outcome
Title Number of Subjects With HbA1C Less Than 6.5%
Hide Description HbA1C was assessed in the subjects 6 months after transplantation and the number of subjects with values less than 6.5% was recorded which indicated better control of blood glucose levels.
Time Frame 6 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The HbA1C for the subject in the abatacept arm was above the threshold (6.5%) for this measure.
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
4 0
4.Secondary Outcome
Title Number of Subjects With HbA1C Levels < 6.5%
Hide Description HbA1C was assessed in the subjects 12 months after transplantation and the number of subjects with levels < 6.5% was recorded which indicated better control of blood glucose levels.
Time Frame 12 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
3 0
5.Secondary Outcome
Title Number of Subjects With HbA1C < 6.5%
Hide Description HbA1C was assessed in the subjects 24 months after transplantation and the number of subjects with levels < 6.5% was recorded which indicated better control of blood glucose levels.
Time Frame 24 months post-transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One participant in the Efalizumab followed by abatacept regimen arm had partial graft function and withdrew from the study at 18 months post-transplantation (prior to this time point of assessment).
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 3 1 0
Measure Type: Number
Unit of Measure: participants
2 0
6.Secondary Outcome
Title Number of Subjects With HbA1C < 6.5%
Hide Description HbA1C was assessed in the subjects 36 months after transplantation and the number of subjects with values < 6.5% was recorded which indicated better control of blood glucose levels.
Time Frame 36 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two participants in the Efalizumab followed by abatacept regimen arm were terminated prior to this time point due to islet graft failure; another one withdrew as they did not want to change to abatacept. The single participant in the Abatacept arm withdrew after graft failure which occurred at 6months post-transplantation.
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 1 0 0
Measure Type: Number
Unit of Measure: participants
1
7.Secondary Outcome
Title Number of Participants With Endogenous Insulin Production Post-transplant, Assessed by Fasting C-peptide Levels
Hide Description The number of subjects exhibiting C-peptide levels ≥ 0.5 ng/mL was recorded.
Time Frame 1, 3, 6, 9,12,18 and 24 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
C-Peptide values were not obtained for 2 participants in the Efalizumab followed by abatacept arm at the 18 and 24 months post-transplant timepoints.
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
1 Month Post-Transplant 4 1
3 Months Post-Transplant 4 0
6 Months Post-Transplant 4 0
9 Months Post-Transplant 4 0
12 Months Post-Transplant 4 0
18 Months Post-Transpla 2 0
24 Months Post-Transplant 2 0
8.Secondary Outcome
Title The Number of Study Participants Exhibiting a Successful Response to a Standard Mixed Meal Test, Measured by Stimulated C-peptide Levels After Islet Transplant.
Hide Description The number of study participants who have detectable C-peptide levels after stimulation from a Mixed Meal Test. An increase of C-peptide indicates that insulin is being released normally in response to food consumption.
Time Frame 1, 3, 6, 9,12,18 and 24 months post-transplantation
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
C-Peptide values were not obtained for 2 participants in the Efalizumab followed by abatacept arm for 18 and 24 months post-transplant
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
1 Month Post-Transplant 4 0
3 Months Post-Transplant 4 0
6 Months Post-Transplant 4 0
9 Months Post-Transplant 3 0
12 Months Post-Transplant 3 0
18 Months Post-Transpla 2 0
24 Months Post-Transplant 2 0
9.Secondary Outcome
Title Number of Subjects With Normal Renal Function, as Measured by Serum Creatinine Levels
Hide Description Renal function was assessed by measuring levels of serum creatinine. Normal values range from 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women.
Time Frame 24 months after transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject in the Efalizumab followed by abatacept regimen arm withdrew from the the study at 18 months post-transplantation and therefore did not have the 24-month assessments.
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description:
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.
Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
Overall Number of Participants Analyzed 4 1 0
Measure Type: Number
Unit of Measure: participants
3 1
Time Frame Adverse events data will be collected from the point of islet transplantation throughout the duration of study participation, an average of 2 years.
Adverse Event Reporting Description All adverse events will be recorded, regardless of the severity or relationship to study medication or procedure unless otherwise stated in the CIT-TCAE v. 3.0. Subjects experiencing adverse events will be treated appropriately and observed at suitable intervals until the events resolve or stabilize.
 
Arm/Group Title Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Hide Arm/Group Description Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received abatacept immunosuppresion regimen after islet-cell transplantation. Participants with Type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.
All-Cause Mortality
Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/4 (50.00%)      0/1 (0.00%)      0/0    
Infections and infestations       
Fever with cough and chills [1]  1/4 (25.00%)  1 0/1 (0.00%)  0 0/0  0
Nervous system disorders       
Vertigo [2]  1/4 (25.00%)  1 0/1 (0.00%)  0 0/0  0
[1]
The participant was hospitalized over night and received IV antibiotics to treat an infection presenting with fever, cough and chills.
[2]
The participant was hospitalized for two days after experiencing vertigo that was progressing in severity. Diagnostic tests were all negative for acute neurological concerns and the participant was released from the hospital.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Efalizumab Followed by Abatacept Regimen Abatacept Regimen Belatacept Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      1/1 (100.00%)      0/0    
Blood and lymphatic system disorders       
Anemia  2/4 (50.00%)  0/1 (0.00%)  0/0 
Leukopenia  1/4 (25.00%)  1/1 (100.00%)  0/0 
Gastrointestinal disorders       
Diarrhea  0/4 (0.00%)  1/1 (100.00%)  0/0 
Hepatobiliary disorders       
Elevated Liver Enzymes  2/4 (50.00%)  1/1 (100.00%)  0/0 
Infections and infestations       
Increased Epstein-Barr Viral load assessed by Polymerase Chain Reaction  3/4 (75.00%)  0/1 (0.00%)  0/0 
Enrollment in this study was limited by the removal of Efalizumab from the market in 2009 after patients (external to this study) being treated for plaque psoriasis were diagnosed with Progressive Multifocal Leukoencephalopathy (PML).
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Nicole Turgeon, MD
Organization: Emory University
Phone: 404-727-3257
Responsible Party: Nicole Turgeon MD, Emory University
ClinicalTrials.gov Identifier: NCT00276250     History of Changes
Other Study ID Numbers: IRB00021852
1136-2005 ( Other Identifier: Emory University )
First Submitted: January 12, 2006
First Posted: January 13, 2006
Results First Submitted: April 25, 2016
Results First Posted: July 27, 2016
Last Update Posted: July 27, 2016