Trial Outcomes & Findings for Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant (NCT NCT01025193)
NCT ID: NCT01025193
Last Updated: 2017-06-12
Results Overview
Before transplant it is necessary to measure antibodies that the recipient might have and compare them to the living or decease donor's immune make-up. Recipients with many antibodies or a specific antibody in a high concentration may have a more difficult time finding a compatible donor, and being transplanted. These recipients are referred to as sensitized patients. It is important that the sensitized recipient and the donor be compatible to prevent rejection after transplant. We measured antibodies levels in sensitized patients waiting for kidney transplant, to see if belimumab would decrease these antibody levels.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
8 participants
Primary outcome timeframe
up to one year pre-transplant
Results posted on
2017-06-12
Participant Flow
From April 2010 to October 2011 patients listed for renal transplant at the Hospital of the University of Pennsylvania who met study inclusion criteria and none of the exclusion criteria were approached during an outpatient clinic visit to participate in the study.
There were no wash out, run-in or transition periods for this trial.
Participant milestones
| Measure |
Belimumab
Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was being used to try to decrease the amount of antibodies in the subject's blood pre-kidney transplant. This use was considered investigational (not approved by the Food and Drug Administration).
Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.
|
|---|---|
|
Overall Study
STARTED
|
8
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Belimumab
Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was being used to try to decrease the amount of antibodies in the subject's blood pre-kidney transplant. This use was considered investigational (not approved by the Food and Drug Administration).
Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.
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|---|---|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Adverse Event
|
3
|
Baseline Characteristics
Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant
Baseline characteristics by cohort
| Measure |
Belimumab
n=8 Participants
Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was used in to try to decrease the amount of antibodies in the pre-kidney transplant patient's blood. This use was considered investigational (not approved by the Food and Drug Administration).
Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
|
Age, Continuous
|
41 years
STANDARD_DEVIATION 26 • n=39 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: up to one year pre-transplantPopulation: any patient who received at least one dose of belimumab was included in analysis population
Before transplant it is necessary to measure antibodies that the recipient might have and compare them to the living or decease donor's immune make-up. Recipients with many antibodies or a specific antibody in a high concentration may have a more difficult time finding a compatible donor, and being transplanted. These recipients are referred to as sensitized patients. It is important that the sensitized recipient and the donor be compatible to prevent rejection after transplant. We measured antibodies levels in sensitized patients waiting for kidney transplant, to see if belimumab would decrease these antibody levels.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.
Patients not experiencing a decrease in antibodies
|
8 Participants
|
|
Effectiveness of Belimumab to Normalize Allo-antibody Levels in Sensitized Patients Awaiting Kidney Transplantation.
Patients experiencing a decrease in antibodies
|
0 Participants
|
PRIMARY outcome
Timeframe: one year pre-transplantPopulation: All participants enrolled who received at least one dose of belimumab were considered for analysis.
In order for a sensitized recipient ( a recipient with antibodies) to be transplanted, the cross match with the donor has to be compatible. We wanted to study if belimumab reduced antibodies in sensitized patients and led those patients to subsequently become cross-match compatible with a donor and allow for successful transplant.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
Kidney transplant as a result of belimumab therapy
|
0 Participants
|
|
Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
kidney transplant unrelated to belimumab therapy
|
1 Participants
|
|
Successful Kidney Transplantation From a Cross-match Compatible Donor (as a Result of Belimumab Therapy)
Kidney transplant not received during trial
|
7 Participants
|
SECONDARY outcome
Timeframe: Belimumab serum drug dilution factors were measured in patients at at timepoints 0 (first day of belimumab), day 14, day 56, day 168, 364, at any unscheduled visits, and at 8 weeks post completion of belimumab therapy.Population: any patient who received at least one dose of belimumab was included in the analysis
We wanted to look at belimumab pharmacokinetics in sensitized patients awaiting kidney transplant. These are reported as number of participants with specific dilution factors at each studied time-point. Blood for these tests could be drawn pre dose as well as 0-4 hours after the dose was given. Belimumab dilutions factors were measured pre dose at timepoints 0 (first day of belimumab), days 56 and 364. Belimumab dilution factors were measured after the dose on days 14, and 168. Belimumab dilution factors were also measured at 8 weeks after completion of belimumab therapy and pre dose at any unscheduled visits if needed.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Pre Dose Belimumab Serum Dilution at 400-Day 0
|
8 Participants
|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Pre Dose Belimumab Serum Dilution at 8000-Day 56
|
7 Participants
|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Pre Dose Belimumab Dilution 8000 at Day 364
|
2 Participants
|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Post Dose Belimumab Dilution at 8000 at Day 14
|
7 Participants
|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Post Dose Belimumab Dilution at 8000 at Day 168
|
6 Participants
|
|
Pharmacokinetics of Belimumab Measured as Number of Participants With Specific Dilution Factors at Each Time Point.
Belimumab Dilution 8000 at 8 weeks After Belimumab
|
2 Participants
|
SECONDARY outcome
Timeframe: 8 weeks after the last dose of belimumabPopulation: Any patient who received at least one dose of belimumab was included in the analysis
B and T Lymphocyte subsets were measured through flow cytometry pre-treatment and at months 1,2,12 and at 8 weeks after the last belimumab dose. We looked for clinically significant changes (as determined by Principal Investigator) in these subsets at each time-point.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
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B and T Lymphocyte Subsets
Decrease in T and B Cell Flow Cytometry:month 1
|
0 Participants
|
|
B and T Lymphocyte Subsets
Decease in T and B Cell Flow Cytometry:month 2
|
0 Participants
|
|
B and T Lymphocyte Subsets
Decrease in T and B Cell Flow Cytometry:month 12
|
0 Participants
|
|
B and T Lymphocyte Subsets
Decrease in T and B Cell Flow Cytometry:post 8 wks
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 8 weeks after completion of therapyPopulation: Any patient who received at least one dose of belimumab was included in the analysis
We assessed for unexpected changes in bound and unbound BLyS levels before and after treatment with belimumab. These were measured from before treatment and at months 1,2,6,10 and 12 months after belimumab treatment and again at 8 weeks after belimumab treatment.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
BLyS Levels Before and After Treatment With Belimumab
Unexpected change in BLyS levels at 1 month
|
0 Participants
|
|
BLyS Levels Before and After Treatment With Belimumab
Unexpected change in BLyS levels at 2 month
|
0 Participants
|
|
BLyS Levels Before and After Treatment With Belimumab
Unexpected change in BLyS levels at 6 mo
|
0 Participants
|
|
BLyS Levels Before and After Treatment With Belimumab
Unexpected change in BLyS levels at 12 months
|
0 Participants
|
|
BLyS Levels Before and After Treatment With Belimumab
Unexpected change in BLyS levels 8 wks post treat
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 12 months of treatment with belimumabPopulation: All patients who received at least one dose of belimumab were included in the analysis
We investigated if belimumab treatment would decrease Hepatitis B vaccine titers by 12 months after treatment with belimumab. All patients received Hepatitis B vaccine before beginning treatment with belimumab.
Outcome measures
| Measure |
Belimumab
n=7 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
Hepatitis B Vaccine Antibody Titers
Patients who maintained Hepatitis B titer
|
7 Participants
|
|
Hepatitis B Vaccine Antibody Titers
Patients who did not maintain Hepatitis B titer
|
0 Participants
|
SECONDARY outcome
Timeframe: up to one year pre-transplantPopulation: Any patient who received at least one dose of belimumab was included in the analysis
To assess the safety of belimumab in sensitized patients awaiting kidney transplant we evaluated the number of participants with serious adverse events possibly or definitely related to belimumab.
Outcome measures
| Measure |
Belimumab
n=8 Participants
Belimumab will be administered intravenously at a dose of 10mg/kg on days 0, 14, 28 and every 28 days for up to 52 weeks to normalize alloantibody levels in sensitized patients awaiting kidney transplantation. Subjects who are not able to undergo transplantation before the end of the treatment period will have final follow-up evaluation 8 weeks after the last dose of belimumab is administered.
Belimumab: Belimumab is a fully human monoclonal antibody that recognizes and inhibits BLyS ®. BLyS ® is a B-lymphocyte stimulator protein which plays a role in the development of B lymphocyte cells into plasma B cells, which then produce antibodies that can sensitize a potential transplant recipient. At the time of this trial, belimumab was not yet FDA approved and was being studied in clinical trials for the treatment of systemic lupus erythematosus. Until this trial, it had not yet been used in the transplant setting.
|
|---|---|
|
Number of Participants With Treatment Related Serious Adverse Events
Hives/infusion reaction related to belimumab
|
1 Participants
|
|
Number of Participants With Treatment Related Serious Adverse Events
No SAEs possibly/definitely related to belimumab
|
7 Participants
|
Adverse Events
Belimumab
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Belimumab
n=8 participants at risk
Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was used to try to decrease the amount of antibodies in the patient waiting for kidney transplant's blood. This use was considered investigational (not approved by the Food and Drug Administration).
Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.
|
|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Cardiac disorders
Atrial Ablation
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Renal and urinary disorders
fluid overload
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Immune system disorders
hives
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Injury, poisoning and procedural complications
Infusion reaction
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
Other adverse events
| Measure |
Belimumab
n=8 participants at risk
Belimumab is a monoclonal antibody. It is the first drug of its type in a new class of medications called BLyS-specific inhibitors. In March 2011, it was approved by the Food and Drug Administration (FDA) for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. In this study, belimumab was used to try to decrease the amount of antibodies in the patient waiting for kidney transplant's blood. This use was considered investigational (not approved by the Food and Drug Administration).
Belimumab : The subjects were given this medication as an outpatient as an intravenous infusion through the arm. The medication was given at the beginning of the study, two weeks later, and then every 4 weeks for up to one year pre-transplant.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash left antecubitus from adhesive tape
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Renal and urinary disorders
Hypertensive episode
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Renal and urinary disorders
Electrolyte imbalance
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
General disorders
non-cardiac related chest pain
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
General disorders
Shakiness
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Blood and lymphatic system disorders
anemia (low red blood cell count)
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Renal and urinary disorders
fluid overload
|
12.5%
1/8 • Number of events 2 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Infections and infestations
infection cold symptoms
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
|
Endocrine disorders
partial parathyroidectomy
|
12.5%
1/8 • Number of events 1 • adverse events were collected for up to 12 months during which patients received belimumab therapy and for 8 weeks after the last dose of belimumab therapy.
|
Additional Information
Jennifer Trofe-Clark
Hospital of the University of Pennsylvania
Phone: 215-614-4274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place