Kidney Transplant Recipient
Conditions
Keywords
Renal Transplant, abatacept
Brief summary
After a kidney transplant, patients take drugs called anti-rejection drugs (immunosuppressives) to prevent their bodies from rejecting the new kidney. At present it is not possible to have a successful transplant without these drugs. These drugs make it possible for a person who receives the transplant to accept the "foreign" kidney. Most patients who get a transplant need to take anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work. Researchers are looking to learn whether abatacept is as good as belatacept in preventing rejection, whether there are other benefits or harms associated with abatacept treatment, and possibly allows greater flexibility on patient's travel and time since abatacept is self-administered at home. This study is being done to answer these questions: Are weekly abatacept injections under the skin a safe and effective substitute for monthly belatacept intravenous (IV) infusions? and How well does the kidney function after switching from belatacept to abatacept?
Detailed description
This is a Phase I, open-label, prospective, single-arm single-center study to evaluate the feasibility, effectiveness, and safety of a regimen substituting subcutaneous abatacept early post-transplant in place of intravenous belatacept as an immunosuppressant in first-time renal transplant recipients. There is a single arm in this study; the Investigational (abatacept) group. Participants will be assigned to a treatment regimen between 2 and 5 months after transplantation. The study drug will be administered until month 12 post-transplant; at that point, all participants will be transitioned to a physician-directed immunosuppressive regimen post-study.
Interventions
DRUGAbatacept 125Mg/Ml Syringe
Participants on a qualifying belatacept regimen (with low-dose tacrolimus, mycophenylate mofetil (MMF), and prednisone) will have their maintenance regimen changed from i.v. Belatacept to s.c. abatacept, which will continue through week 52 (month 12) post-transplant: Costimulation blockade: \- Abatacept 125 mg subcutaneous weekly
Sponsors
Idelberto Badell
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Must be able to understand and provide informed consent. * Male or Female, 18-70 years of age at the time of enrollment (all races and ethnicities) * Negative crossmatch (virtual or physical) at the time of transplant * No less than 8 weeks, no more than 20 weeks post-transplant at enrollment * A first-time renal transplant who has been treated with belatacept from the time of transplant, receiving tacrolimus (target trough 3-5 ng/ml), mycophenolate mofetil (or mycophenolic acid or azathioprine), prednisone (also see
Exclusion criteria
). * eGFR ≥ 40ml/min/m2 \[using 2021 the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\]. * Prior documented evidence of Epstein-Barr virus (EBV) seropositivity must be available. * Female study participants of childbearing potential must have a negative pregnancy test before enrollment. * Agreement to use contraception that is more than 80% effective. * Vaccines are current as per the Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials. * Study participants must have a negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved Interferon Gamma Release Assay (IGRA) blood test, such as QuantiFERON®-Gold tuberculosis (TB) or T-SPOT®-TB assay. PPD or IGRA testing must be documented to have been performed within the 52 weeks before enrollment. Patients with latent TB may become eligible after completion of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Are Compliant With Self-administration | Up to 12 months post-transplantation, an average of 8 months | Compliance and self-administration will be measured using the abatacept administration logs and autoinjector accountability. |
| Number of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated Rejection (aTCMR) or Antibody-mediated Rejection (ABMR) as Defined by Banff Criteria at or Before 12 Months After Transplantation. | Up to 12 months post-transplantation, an average of 8 months | For-cause biopsies may be performed as dictated by the clinical team. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator. |
| Number of Participants Presenting Serious Adverse Events | Up to 12 months post-transplantation, an average of 8 months | Assessments of serious adverse events will be completed at each study visit from the time abatacept starts through 12 months post-transplant. |
| Number of Participants With Serious Infections | Up to 12 months post-transplantation, an average of 8 months | Any serious infection requiring hospitalization or prolonged therapy, including but not limited to treatment ≥ 20 days, will be documented. |
| Number of Patients With Cytomegalovirus (CMV) Viremia Stratified by the Magnitude | Up to 12 months post-transplantation, an average of 8 months | All subjects will be monitored for CMV infection by quantitative polymerase chain reaction (PCR) in the blood per the Emory Transplant Center standard of care protocol, CMV viremia stratified by count ≥35 but \<10,000 or ≥ 10,000. |
| Number of Patients With BK Viremia Stratified by the Magnitude | Up to 12 months post-transplantation, an average of 8 months | Undetected, \>0 but \< 1,000, ≥ 1,000 but \<10,000, or ≥ 10,000 - 100,000, ≥100,000 or stratified by log, which is reported as a result. |
| Number of Participants Who Develop Any Malignancy | Up to 12 months post-transplantation, an average of 8 months | Incidence of any malignancy, including Post-Transplant Lymphoproliferative Disorder (PTLD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing the Composite Outcome of Death or Allograft Failure | Up to 12 months post-transplantation, an average of 8 months | Death and/or allograft failure at or before 12 months after transplantation |
| Number of Participants With Biopsy-proven Acute T-cell Mediated Cellular Rejection (BP-aTCMR) | Up to 12 months post-transplantation, an average of 8 months | Incidence of biopsy-proven acute T-cell mediated cellular rejection (BP-aTCMR) |
| Number of Participants Treated for Rejection | Up to 12 months post-transplantation, an average of 8 months | The number of participants treated for rejection with any of the following: i) corticosteroids within 12 months, ii) T-cell depleting therapy within 12 months, iii) any other treatment for rejection within 12 months of transplantation |
| Number of Participants Treated for Acute Rejection Due to Clinical Suspicion Rather Than BP-aTCMR or BP-aABMR Within 12 Months of Transplantation. | Up to 12 months post-transplantation, an average of 8 months | For-cause biopsies may be performed as dictated by the clinical team. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator. |
| Number of Participants With Biopsy-proven Active Antibody-mediated Rejection (BP-aABMR) | Up to 12 months post-transplantation, an average of 8 months | For-cause biopsies may be performed as dictated by the clinical team. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator. |
| Number of Participants With Changes in Allograft Biopsies for the 5 Categories of aTCMR Specified in the Banff Schema | Up to 12 months post-transplantation, an average of 8 months | For-cause biopsies may be performed as dictated by the clinical team. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator. |
| Time to Changes in Allograft Biopsies for the 5 Categories of aTCMR Specified in the Banff Schema | Up to 12 months post-transplantation, an average of 8 months | Calculations will be made from the start of abatacept through to 12 months post-transplant. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator. |
| Number of Participants Who Develop De-novo Donor Specific Antibody (DSA) | Up to 12 months post-transplantation, an average of 8 months | Number of participants who develop de-novo DSA |
| Estimated Glomerular Filtration Rate (eGFR) | Baseline and 12 months post-transplantation | The eGFR will be calculated at the time abatacept is started and 12 months post-transplant |
| Number of Days to Events [TCMR, ABMR, De-novo Specific Antibodies (DSA) Formation, Graft Loss]. | Up to 12 months post-transplantation, an average of 8 months | All events will be documented, and calculations will be made from the start of abatacept through 12 months post-transplant. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIdelberto R Badell, MD
Emory University
Participant flow
Recruitment details
Participants were recruited from Emory Healthcare of Atlanta in Atlanta, Georgia, USA. Participant enrollment began August 2, 2023, and all follow-up was complete by February 14, 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 14 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 1 / 14 |
| serious Total, serious adverse events | 1 / 14 |
Outcome results
None listed