Trial Outcomes & Findings for Belatacept Post Depletional Repopulation to Facilitate Tolerance (NCT NCT00565773)
NCT ID: NCT00565773
Last Updated: 2020-02-11
Results Overview
The primary endpoint is the number of patients successfully withdrawn from oral immunosuppression (sirolimus) for one year after their last dose of sirolimus.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.
COMPLETED
PHASE2
40 participants
Year 2
2020-02-11
Participant Flow
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.
Participant milestones
| Measure |
Immunosuppresive Medication Combination
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 Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Immunosuppresive Medication Combination
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 Study
Withdrawal by Subject
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Belatacept Post Depletional Repopulation to Facilitate Tolerance
Baseline characteristics by cohort
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Age, Continuous
|
46.5 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
40 Participants
n=99 Participants
|
|
Also received a bone marrow transfusion
|
9 Participants
n=99 Participants
|
|
Type of Transplant
Living donor transplant
|
30 Participants
n=99 Participants
|
|
Type of Transplant
Deceased donor transplant
|
10 Participants
n=99 Participants
|
|
Body Mass Index (BMI)
|
26.0 kg/m^2
n=99 Participants
|
PRIMARY outcome
Timeframe: Year 2Population: This analysis includes participants meeting criteria to wean from sirolimus who also opted to attempt sirolimus weaning.
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.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=19 Participants
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.
|
|---|---|
|
Number of Patients Successfully Withdrawn From Oral Immunosuppression
Successful weaning
|
12 Participants
|
|
Number of Patients Successfully Withdrawn From Oral Immunosuppression
Failed weaning
|
7 Participants
|
SECONDARY outcome
Timeframe: Year 1, Year 3, Year 5Population: Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
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.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Number of Participants Experiencing Costimulation Blockade-resistant Rejection (CoBRR)
Year 1
|
0 Participants
|
|
Number of Participants Experiencing Costimulation Blockade-resistant Rejection (CoBRR)
Year 3
|
0 Participants
|
|
Number of Participants Experiencing Costimulation Blockade-resistant Rejection (CoBRR)
Year 5
|
0 Participants
|
SECONDARY outcome
Timeframe: Year 1, Year 3, Year 5Population: Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
Assessment of biopsy proven chronic allograft nephropathy at 1, 3 and 5 years post-transplant is presented as the number of participants experiencing CAN.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Number of Participants Experiencing Chronic Allograft Nephropathy (CAN)
Year 1
|
0 Participants
|
|
Number of Participants Experiencing Chronic Allograft Nephropathy (CAN)
Year 3
|
0 Participants
|
|
Number of Participants Experiencing Chronic Allograft Nephropathy (CAN)
Year 5
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Year 5The number of participants experiencing BK viremia, an opportunistic infection, during the study is presented here.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Number of Participants With BK Viremia
|
17 Participants
|
SECONDARY outcome
Timeframe: Up to Year 5Long 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).
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Number of Participants Developing Donor-specific Alloantibody (DSA)
|
5 Participants
|
SECONDARY outcome
Timeframe: Year 1, Year 3, Year 5Population: Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
The number of participants whose grafts survived without graft failure at each follow up time point is presented here.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Number of Participants With Surviving Grafts
Year 3
|
40 Participants
|
|
Number of Participants With Surviving Grafts
Year 1
|
40 Participants
|
|
Number of Participants With Surviving Grafts
Year 5
|
36 Participants
|
SECONDARY outcome
Timeframe: Year 1, Year 3, Year 5Population: Between the 3 and 5 year assessments, one participant was removed for no longer meeting eligibility criteria and one participant withdrew from the study.
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.
Outcome measures
| Measure |
Immunosuppresive Medication Combination
n=40 Participants
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.
|
|---|---|
|
Estimated Glomerular Filtration Rate (eGFR)
Year 1
|
70 mL/min/1.73m^2
Standard Deviation 23
|
|
Estimated Glomerular Filtration Rate (eGFR)
Year 3
|
67 mL/min/1.73m^2
Standard Deviation 21
|
|
Estimated Glomerular Filtration Rate (eGFR)
Year 5
|
71 mL/min/1.73m^2
Standard Deviation 19
|
Adverse Events
Immunosuppresive Medication Combination
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Immunosuppresive Medication Combination
n=40 participants at risk
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.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Shingles
|
5.0%
2/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
Skin and subcutaneous tissue disorders
HHV-8/Kaposi's sarcoma
|
2.5%
1/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
Surgical and medical procedures
Incisional hernia
|
5.0%
2/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
Skin and subcutaneous tissue disorders
Mouth ulcers (sirolimus-associated)
|
22.5%
9/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
Cardiac disorders
Pericardial effusion
|
2.5%
1/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
General disorders
Edema
|
7.5%
3/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
2/40 • Information on adverse events were collected from the time of initiation of the investigational product through the 5 year follow up visit.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place