Kidney Failure, Chronic
Conditions
Keywords
Chronic allograft failure, Kidney Transplantation
Brief summary
The purpose of this study is to test the safety and effectiveness of everolimus (Zortress®) in preventing antibody formation in patients with chronic failing kidney transplants. Everolimus (Zortress®) is approved by the U.S. Food and Drug Administration for the prevention of rejection in kidney transplant. The primary objective for the study is to determine whether conversion of patients with chronic renal graft failure approaching dialysis to an everolimus-based regimen will prevent allosensitization. The secondary objective will be to determine whether conversion of patients with chronic renal graft failure to everolimus (elimination of calcineurin inhibitor) will delay the onset of dialysis.
Interventions
DRUGEverolimus
Everolimus will initially be dosed at 0.75 mg tablet taken orally twice a day. The dose will be adjusted to maintain serum trough concentrations of 5-8 ng/ml.
Sponsors
Novartis Pharmaceuticals
Ashtar Chami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* recipient of deceased or living donor kidney transplant * Age 18-75 years (inclusive) * Male or female * renal allograft dysfunction/deterioration evidenced by glomerular filtration rate (GFR) less than or equal to 35 * Grade 2 or 3 Interstitial fibrosis/tubular atrophy (IF/TA) on renal allograft biopsy within 5 years of enrollment * Willing and able to provide informed consent for study participation
Exclusion criteria
* Prior solid organ transplant (other than kidney) * History of donor-specific antibody * History of biopsy-proven acute rejection within 1 year prior to enrollment * Proteinuria greater than or equal to 1.5 gm on spot urine protein/creatinine ratio * Evidence of Hepatitis C virus infection (antibody positive or polymerase chain reaction(PCR) positive) * Epstein Barr Virus (EBV) or cytomegalovirus (CMV) viremia at the time of enrollment * Subjects receiving belatacept (Nulojix) * Pregnant or nursing (lactating) women * Women of child-bearing potential (WOCBP) who are unwilling or unable to use two birth-control methods throughout participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Fluorescence Index (MFI) of Donor Specific Alloantibodies (DSA) | 36 months | Development of new donor-specific alloantibody as determined by solid phase bead array (Luminex) technology defining MFIs for fine specificity at Class I and Class II antigens (human leukocyte antigens (HLA) - A, B, C, DR, DP, and DQ) with an MFI \>5000 defined as positive |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Return to Dialysis Dependence | 36 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Everolimus Conversion Subjects who have previously undergone a kidney transplant and were in late stage renal allograft failure were randomized to take everolimus at least 0.75 mg twice daily after discontinuing current calcineurin inhibitor. Subjects were weaned off of all other immunosuppression medicines when dialysis started. | 1 |
| Control Subjects who have previously undergone a kidney transplant and were in late stage renal allograft failure were randomized to continue on current immunosuppressive regimen. Subjects were weaned off of all immunosuppression medicines when dialysis started. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Everolimus Conversion | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 1 / 1 | 0 / 0 |
Outcome results
Primary
Mean Fluorescence Index (MFI) of Donor Specific Alloantibodies (DSA)
Development of new donor-specific alloantibody as determined by solid phase bead array (Luminex) technology defining MFIs for fine specificity at Class I and Class II antigens (human leukocyte antigens (HLA) - A, B, C, DR, DP, and DQ) with an MFI \>5000 defined as positive
Time frame: 36 months
Population: Single subject enrolled was terminated early. Data analysis was not performed as the Month 36 visit did not occur.
Secondary
Incidence of Return to Dialysis Dependence
Time frame: 36 months
Population: Single subject enrolled was terminated early. Data analysis was not performed as the Month 36 visit did not occur.