Renal Transplant Recipient
Conditions
Keywords
Renal transplant
Brief summary
This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function.The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.
Detailed description
This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function. Research subjects will be recruited from those who were initiated on belatacept at the time of their kidney transplant and have been stable on belatacept therapy for at least 2 years post-transplant and off CNI therapy for at least 6 months. A total of 86 subjects will be randomized in equal numbers, 43 patients in each arm. Enrollment of all 86 patients is expected to be completed within 1.5 years. All patients will be actively followed in the study for 24 months following randomization. The patient participation is projected to last a total of 3.5 years with data analysis to follow. The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.
Interventions
DRUGBelatacept
Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg monthly
DRUGAbatacept
Abatacept is an immunosuppressive medication and will be given SQ at a dose of 125 mg s.c. weekly
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, randomized controlled non-inferiority trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Individuals who meet all of the following criteria are eligible for enrollment as study participants: 1. Adult (age ≥18 years currently) 2. First-time renal transplant recipients of either living donor or deceased donor 1. Treatment with belatacept from the time of transplant 2. At least 2 years post-transplant and off CNI therapy for at least 6 months 3. Patients at low immunologic risk 1. First time transplant 2. HLA antibody screen with PRA \< 80% against class I and class II antigens 3. Negative crossmatch (actual or virtual) 4. No donor specific anti-HLA antibody (DSA) 5. No more than one episode of rejection (Banff grade 1A or greater) 6. No episodes of rejection (borderline or greater) within the last 6 months prior to study participation 7. No rejection of Banff grade IIB or greater 4. Immunosuppression consisting of belatacept (5mg/kg q 1M), mycophenolate mofetil (at least 1000 mg daily), or equivalent mycophenolic acid (720 mg daily) or azathioprine (1- 2 mg/kg daily) dose, and prednisone 5 mg daily. 5. Confirmed Tb screening at the time of transplantation
Exclusion criteria
Individuals who meet any of these criteria are not eligible for enrollment as study participants: 1. Repeat renal transplant, or multi-organ transplant recipient 2. History of more than one episode of biopsy-proven acute rejection (Banff grade 1A or greater), or of any episode of rejection of Banff 97 grade IIB or greater, or any rejection (borderline or greater) within the last 6 months 3. Pregnancy (women of childbearing potential must use adequate contraception during study) 4. GFR less than 35 5. Serum creatinine at enrollment more than 30% higher than at 3 months (±4 weeks) prior to randomization 6. Recent history of clinically significant proteinuria (urinary protein/Cr ratio \>1.0) 7. Receiving belatacept at a dose other than 5 mg/kg body weight 8. Receiving mycophenolate mofetil at a dose of less than 1000 mg po QD (or mycophenolic acid or azathioprine equivalent). 9. Receiving prednisone at a dose greater than 5 mg po qd within 3 months of enrollment 10. Not currently receiving maintenance immunosuppression with prednisone 11. Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization 12. Evidence of CMV viremia or clinical CMV infection within the last 3 months prior to randomization. 13. BK viremia of greater than 4.3 DNA log copies/mL (greater than 20,000 copies/mL) within 3 months of randomization 14. Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required) 15. Known HIV-positivity (testing not required) 16. Presence of donor specific antibody by Luminex single antigen bead assay, or antibody screen (% PRA) above 80%. 17. History of substance abuse or psychiatric disorder not compatible with study adherence and follow up. 18. History of medical noncompliance 19. Untreated latent Tb (as determined from prior Tb screening at the time of transplantation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean estimated GFR (eGFR) between randomization and 12 months post baseline | Baseline, 12 months post baseline | Difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in eGFR between abatacept and belatacept groups at 24 months | Monthly until 24 months post baseline | The treatment difference in eGFR between abatacept and belatacept groups at 24 months, using a monthly repeated measures model and a pre-specified acceptable difference, or non-inferiority margin of 5 ml/min/1.73m2. |
| Number of subjects with biopsy proven acute rejection: Acute Cellular Rejection (ACR) | 12 months post baseline, 24 months post baseline | Incidence and severity of acute cellular rejection (ACR) |
| Number of subjects with biopsy proven acute rejection: Antibody Mediated Rejection (AMR) | 12 months post baseline, 24 months post baseline | Incidence and severity of antibody mediated rejection (AMR) analyses |
| Number of participants with kidney transplant biopsies post baseline | 12 months post baseline, 24 months post baseline | Number of participants with kidney transplant biopsies post baseline |
| Proportion of subjects treated for ACR/AMR due to clinical suspicion | 12 months post baseline, 24 months post baseline | Proportion of subjects treated for ACR/AMR due to clinical suspicion |
| Number of subjects with de novo anti-donor human leukocyte antigen (HLA) antibodies | 12 months post baseline, 24 months post baseline | Incidence of de novo anti-donor human leukocyte antigen (HLA) antibodies |
| First occurrence of graft loss or death post baseline | 12 months post baseline, 24 months post baseline | First occurrence of graft loss or death at 6, 12 and 24 months post baseline |
| Number of deaths at 6, 12 and 24 months post baseline | 12 months post baseline, 24 months post baseline | Incidence of death with graft function at 6, 12 and 24 months post baseline |
| Incidence of death-censored graft loss post baseline | 12 months post baseline, 24 months post baseline | Incidence of death-censored graft loss at 12 and 24 months |
| Compliance with patient-administered subcutaneous abatacept | 12 months post baseline, 24 months post baseline | Compliance with patient-administered subcutaneous abatacept |
| Incidence of adverse events | 12 months post baseline, 24 months post baseline | Incidence of adverse events |
| Incidence of serious adverse events | 12 months post baseline, 24 months post baseline | Incidence of serious adverse events |
| Incidence of events of special interest | 12 months post baseline, 24 months post baseline | Incidence of events of special interest, including CMV viremia, BKV viremia, and serious infections |
| Incidence of any malignancy | 12 months post baseline, 24 months post baseline | Incidence of any malignancy including PTLD |
| Incidence of subcutaneous injection site complications | 12 months post baseline, 24 months post baseline | Incidence of subcutaneous injection site complications |
| Proportion of subjects who develop de-novo, anti-HLA donor specific antibody | 12 months post baseline, 24 months post baseline | Proportion of subjects who develop de-novo, anti-HLA donor specific antibody |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIdelberto R Badell, MD
Emory University
Outcome results
None listed