Kidney Transplantation
Conditions
Keywords
Immunosuppression, Transplantation Immunology
Brief summary
The purpose of this study is to transition patients who have been stable on Belatacept for one year after kidney transplant from standard 4-week to an investigational 8-week belatacept dosing schedule. The investigators hypothesize that renal function and acute rejection rates will be non-inferior with 8-week belatacept dosing.
Detailed description
The current dosing protocol for patients who have undergone a kidney transplant requires that Belatacept be given as an infusion every 4 weeks. The investigator wants to assess if the patients who have been stable for one year after transplant can be safely transitioned to an 8-week Belatacept infusion schedule. Renal function and any episodes of acute rejection will be closely monitored.
Interventions
DRUGBelatacept
Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg at 4-weekly or 8-weekly intervals.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (age ≥18 years currently), * First-time renal transplant recipients of either living donor or deceased donor, 1. who were initiated on belatacept at the time of transplant and 2. are at least one year post-transplant and off CNI therapy for at least 6 months. * Patients at low immunologic risk, defined as 1. patients with a first transplant who have a PRA \< 50 against class I and class II antigens, 2. no DSA (donor-specific antibodies), 3. who have not had more than one episode of rejection, and 4. no episodes of rejection within the last 6 months prior to enrollment, and 5. no rejection with a grade of IIB or above.
Exclusion criteria
* Not first renal transplant, or multi-organ transplant recipient * History of greater than one episode of biopsy-proven acute rejection, or of rejection of Banff 97 grade IIB or greater, or rejection within the last 6 months. * Pregnancy (women of childbearing potential must use adequate contraception during study) * Unwilling to receive all belatacept infusions at the Emory Transplant Center * Calculated Glomerular Filtration Rate (GFR) less than 35. * Serum creatinine at enrollment over 30% higher than 3 months (±4 weeks) prior to randomization * HbA1C greater than 8 at enrollment * Recent history of significant proteinuria (protein/Cr ratio \>1) * Non-standard belatacept dosing (e.g. dose other than 5 mg belatacept/kg body weight) * Cellcept dose less than 500 mg po bid. * Prednisone dose greater than 5mg po qd within 3 months of randomization * Patients not currently taking prednisone * Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization * Evidence of Cytomegalovirus (CMV) viremia or clinical CMV infection within last 3 months. * Polyomavirus BK PCR (polymerase chain reaction) load greater then 4.3 (copy number greater than 20,0000) within 3 months of randomization * Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required) * Known HIV (human immunodeficiency virus infection) (testing not required) * Presence of donor specific antibody by Luminex single antigen assessment, or panel reactivity (PRA) above 50%. * History of substance abuse or psychiatric disorder not compatible with study adherence and follow up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline | 12 months from baseline | The mean estimated Glomerular Filtration Rate (eGFR) will be calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine measurements and the patient's age, gender, and race. An eGFR below 60 ml/min/1.73 m\^2 indicates lower renal function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline | 6 months post baseline, 12 months post baseline | The number of occurrences of transplant rejection at 6 months and 12 months from baseline will be recorded. |
| Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline, 12 months post baseline | The number of subjects with Grade IIA and lower severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells. |
| Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline, 12 months post baseline | The number of subjects with Grade IIB and higher severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells. |
| Number of Deaths at 6 Months and 12 Months Post Baseline | 6 months post baseline, 12 months post baseline | The total number of subject deaths at 12 months from baseline will be recorded. |
| Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline | 6 months post baseline, 12 months from baseline | The total number of subjects who experienced death censored graft loss at 6 months and 12 months from baseline will be recorded. |
| Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline | 6 moths post baseline, 12 months post baseline | The number of subjects who have circulating human leukocyte antigen donor specific antibodies (HLA DSA) at 12 months from baseline will be recorded. |
| Number of Clinic Visits | At 12 months from baseline | The number of clinic visits by the subjects at the end of 12 months from baseline will be recorded. |
| Number of Subjects Needing Hospitalizations | At 12 months from baseline | The number of subjects who had hospitalizations at the end of 12 months from baseline will be recorded |
| Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline | 12 months post baseline | The number of subjects needing transplant biopsies at 12 months from baseline will be recorded. |
| Cost Analysis | At 12 months from baseline | The mean total cost of infusions received by each subject and those associated with round trip travel to the Emory Transplant Center (ETC) will be estimated using the distance between the residential addresses of subjects and the ETC. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belatacept 8-weekly Subjects who are stable on belatacept therapy at least one year after a renal transplant will receive belatacept infusion intravenously (IV) at 5 mg/kg every 8 weeks.
Belatacept: Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg at 4-weekly or 8-weekly intervals. | 81 |
| Belatacept 4-weekly Subjects who are stable on belatacept therapy at least one year after a renal transplant will receive belatacept infusion intravenously (IV) at 5 mg/kg every 4 weeks.
Belatacept: Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg at 4-weekly or 8-weekly intervals. | 82 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Belatacept 8-weekly | Belatacept 4-weekly | Total |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 13 | 52 years STANDARD_DEVIATION 12 | 51 years STANDARD_DEVIATION 12.7 |
| Race/Ethnicity, Customized African American | 36 Participants | 32 Participants | 68 Participants |
| Race/Ethnicity, Customized Non African American | 45 Participants | 50 Participants | 95 Participants |
| Region of Enrollment United States | 81 participants | 82 participants | 163 participants |
| Sex: Female, Male Female | 27 Participants | 19 Participants | 46 Participants |
| Sex: Female, Male Male | 54 Participants | 63 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 2 / 76 |
| other Total, other adverse events | 23 / 81 | 27 / 82 |
| serious Total, serious adverse events | 9 / 81 | 10 / 82 |
Outcome results
Primary
Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline
The mean estimated Glomerular Filtration Rate (eGFR) will be calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine measurements and the patient's age, gender, and race. An eGFR below 60 ml/min/1.73 m\^2 indicates lower renal function.
Time frame: 12 months from baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Belatacept 8-weekly | Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline | 72.13 ml/min/1.73m^2 |
| Belatacept 4-weekly | Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline | 72.65 ml/min/1.73m^2 |
Secondary
Cost Analysis
The mean total cost of infusions received by each subject and those associated with round trip travel to the Emory Transplant Center (ETC) will be estimated using the distance between the residential addresses of subjects and the ETC.
Time frame: At 12 months from baseline
Population: Resources/tools not available for recording/tracking the data required to reliably report the outcome.
Secondary
Number of Clinic Visits
The number of clinic visits by the subjects at the end of 12 months from baseline will be recorded.
Time frame: At 12 months from baseline
Population: Resources/tools not available for recording/tracking the data required to reliably report the outcome.
Secondary
Number of Deaths at 6 Months and 12 Months Post Baseline
The total number of subject deaths at 12 months from baseline will be recorded.
Time frame: 6 months post baseline, 12 months post baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Deaths at 6 Months and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
| Belatacept 8-weekly | Number of Deaths at 6 Months and 12 Months Post Baseline | 12 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Deaths at 6 Months and 12 Months Post Baseline | 6 months post baseline | 1 Participants |
| Belatacept 4-weekly | Number of Deaths at 6 Months and 12 Months Post Baseline | 12 months post baseline | 2 Participants |
Secondary
Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline
The number of occurrences of transplant rejection at 6 months and 12 months from baseline will be recorded.
Time frame: 6 months post baseline, 12 months post baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline | 6 months post baseline | 3 Participants |
| Belatacept 8-weekly | Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline | 12 months post baseline | 4 Participants |
| Belatacept 4-weekly | Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline | 12 months post baseline | 2 Participants |
| Belatacept 4-weekly | Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline | 6 months post baseline | 1 Participants |
Secondary
Number of Subjects Needing Hospitalizations
The number of subjects who had hospitalizations at the end of 12 months from baseline will be recorded
Time frame: At 12 months from baseline
Population: Resources/tools not available for recording/tracking the data required to reliably report the outcome.
Secondary
Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline
The number of subjects needing transplant biopsies at 12 months from baseline will be recorded.
Time frame: 12 months post baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept 8-weekly | Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline | 5 Participants |
| Belatacept 4-weekly | Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline | 2 Participants |
Secondary
Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline
The total number of subjects who experienced death censored graft loss at 6 months and 12 months from baseline will be recorded.
Time frame: 6 months post baseline, 12 months from baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
| Belatacept 8-weekly | Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline | 12 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline | 12 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
Secondary
Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline
The number of subjects with Grade IIA and lower severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells.
Time frame: 6 months post baseline, 12 months post baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline | 3 Participants |
| Belatacept 8-weekly | Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline | 12 months post baseline | 4 Participants |
| Belatacept 4-weekly | Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline | 1 Participants |
| Belatacept 4-weekly | Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline | 12 months post baseline | 2 Participants |
Secondary
Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline
The number of subjects with Grade IIB and higher severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells.
Time frame: 6 months post baseline, 12 months post baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
| Belatacept 8-weekly | Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline | 12 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline | 12 months post baseline | 0 Participants |
Secondary
Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline
The number of subjects who have circulating human leukocyte antigen donor specific antibodies (HLA DSA) at 12 months from baseline will be recorded.
Time frame: 6 moths post baseline, 12 months post baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belatacept 8-weekly | Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline | 6 months post baseline | 2 Participants |
| Belatacept 8-weekly | Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline | 12 months post baseline | 3 Participants |
| Belatacept 4-weekly | Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline | 6 months post baseline | 0 Participants |
| Belatacept 4-weekly | Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline | 12 months post baseline | 0 Participants |