Renal Transplant Recipients With Anti-HLA Antibodies
Conditions
Brief summary
The purpose of this treatment registry study is to determine if monthly infusions of Intravenous Immunoglobulin (IVIg) for 6 months will neutralize donor specific antibodies that are thought to be responsible for chronic rejection episodes in renal transplant subjects. 162 renal transplant subjects will receive IVIg 5% at 2gm/kg/month for 6 months and be followed for 3 years.
Interventions
None listed
Sponsors
Octapharma
Databean
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is 18 years of age or older * Able to provide voluntary written informed consent * Renal transplant recipient at least 1 month post-transplant * On stable doses of maintenance immunosuppression for at least 14 days prior to study entry and remains on stable maintenance doses for the duration of the study * Presence of DSA greater than or equal to 1000 mean fluorescence intensity (MFI) single antigen bead assay via Luminex (normalized 2,000 - 15,000 MFI, inclusive) measured within 6 months prior to consent * Female subjects must be post-menopausal for at least 1 year, or surgically sterilized, or must agree to use two effective methods of birth control from the time of consent through 30 days after the last dose of IVIg. * Male subjects must be surgically sterilized, or must agree to use two effective methods of birth control from the time of consent through 30 days after the last dose of IVIg * Subject is compliant and intends to be available for follow-up study period of 3 years
Exclusion criteria
* Multi-organ transplant * History of anaphylactic or severe systemic reactions to human immunoglobulin * IgA deficient subjects with antibodies against IgA and a history of hypersensitivity * Serum creatinine \> 3.0 mg/dL within 90 days prior to consent * Recipients of ABO incompatible kidney transplants * Acute rejection within 180 days (6 months) prior to consent defined as: 1. Biopsy proven acute Cellular Rejection \[Banff grade I (including IA and IB), grade II (including IIA and IIB) or grade III\]; or 2. an antibody-mediated rejection with C4d positivity, or 3. chronic rejection with C4d positivity (C4d positivity is defined as staining diffuse in peritubular capillary area. Isolated C4d glomerular staining or C4d staining of \< 50% of the peritubular capillaries will not be
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in mean change from screening to 36 months in graft survival and glomerular filtration rates (GFR) | 3 years | Success is defined as: Allograft survival as compared to the performance goal (PG) at 36 months. For the purposes of this study, a graft will be presumed to be lost is when a subject is started on dialysis and is not able to subsequently be removed from dialysis; or a subject's serum creatinine reaches 4.0 mg/dL, is sustained for \>48hours and is not thought to be due to other causes; or the subject is re-transplanted; or the subject dies. AND: A change in extended GFR, defined as \<15% decrease in mean GFR from baseline to 36 months |
Secondary
| Measure | Time frame |
|---|---|
| Allograft Survival | 3 years |
Other
| Measure | Time frame |
|---|---|
| Proportion of subjects that achieve a complete response defined as a return of DSAmax antibody MFI to less than 2000 at 9 months | 3 years |
| Allograft survival in subjects with preformed DSA defined as an MFI > 500 at the time of transplantation | 3 years |
| Change in proteinuria from screening to 1, 2, and 3 years | 3 years |
| A difference in mean change of extended GFR ml/min/1.73 m2 (eGFR - MDRD) | 3 years |
| Incidence of proteinuria (urine protein:creatinine > 1.5) at 1, 2 and 3 years | 3 years |
| Allograft survival in subjects who are recipients of >1 renal transplant | 3 years |
| Change in serum creatinine from screening to 1, 2, and 3 years | 3 years |
Countries
United States
Outcome results
None listed