Early Substitution of Subcutaneous Abatacept for Belatacept as Costimulation Blockade to Minimize Calcineurin Inhibitors (CNI) Exposure After Kidney Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Number of Participants Who Are Compliant With Self-administration
研究概览
简要总结
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?
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •Exclusion Criteria:
- •Inability or unwillingness of a study participant to give written informed consent or comply with the study protocol.
- •Recipient of previous organ transplant of any type.
- •Multi-organ transplant.
- •Calculated Panel Reactive Antibody (cPRA) >80 at the time of enrollment.
- •History of any episode of biopsy-proven Banff rejection (including borderline rejection or any grade of acute TCMR) before enrollment.
- •History of any malignancy including lymphoma within 5 years of enrollment. Study participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled.
- •Any past or current issue which in the opinion of the investigator may pose additional risks to the participant in the study, may interfere with the study participant's ability to comply with the study requirements, or may impact the quality or interpretation of the data obtained from the study.
- •Human immunodeficiency virus (HIV): individuals known to be HIV positive.
- •Hepatitis C virus (HCV): any study participant who receives a kidney from a seropositive or HCV RNA PCR-positive donor is ineligible. Any study participant who was HCV RNA PCR positive at transplant is ineligible. Any study participant with a history of HCV seropositivity or HCV infection who has not met the criteria for sustained spontaneous clearance or sustained viral response to therapy is ineligible.
- •Hepatitis B virus (HBV): Individuals with any of the following are NOT eligible:
- •Recipient or donor positive for hepatitis B surface antigen (HBsAg)
- •Recipient or donor positive for antibodies to hepatitis B core antigen (anti-HBc)
- •Recipient or donor is known to have had a positive HBV DNA PCR
- •Evidence of CMV viremia or clinical CMV infection at any time after transplant.
- •Kidney recipients who were CMV seronegative who received an organ from a CMV seropositive donor.
- •BK viremia of greater than 4.3 DNA log copies/ml (greater than 20,000 copies/ml) at any time post-transplant.
- •Active uncontrolled infection within 1 month of enrollment.
- •Clinically significant proteinuria (urinary protein/Cr ratio >1.0).
- •Receiving belatacept at a dose other than 5 mg/kg body weight.
- •Receiving mycophenolate mofetil at a dose of less than 1000 mg daily (or mycophenolic acid or azathioprine equivalent).
- •Receiving prednisone at a dose greater than 5 mg daily.
- •Presence of donor-specific antibody by Luminex single antigen bead assay.
研究组 & 干预措施
Abatacept
Participants on a qualifying belatacept regimen will have their maintenance regimen changed from i.v. Belatacept to s.c. abatacept. 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.
干预措施: Abatacept 125Mg/Ml Syringe (Drug)
结局指标
主要结局
Number of Participants Who Are Compliant With Self-administration
时间窗: 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.
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Up to 12 months post-transplantation, an average of 8 months
Incidence of any malignancy, including Post-Transplant Lymphoproliferative Disorder (PTLD)
The proportion of subjects who tolerate subcutaneous injections and are compliant with self-administration
时间窗: Throughout the study intervention (up to 12 months)
Measured by abatacept administration logs and autoinjector accountability.
Incidence of serious infection of special interest
时间窗: Throughout the study intervention up to 12 months post transplant
Any infection requiring hospitalization or prolonged therapy, including but not limited to treatment ≥ 20 days)
Incidence of any malignancy
时间窗: Throughout the study intervention up to 12 months post transplant
Incidence of any malignancy including Post-Transplant Lymphoproliferative Disorder (PTLD)
The proportion 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.
时间窗: Throughout the study intervention up to 12 months post transplant
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.
The cumulative incidence of serious adverse events
时间窗: Throughout the study intervention up to 12 months post transplant
Assessments for the development of serious adverse events will be completed at each study visit.
Incidence of patients with cytomegalovirus (CMV) viremia stratified by the magnitude
时间窗: Throughout the study intervention up to 12 months post transplant
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 protocolCMV viremia stratified by count ≥35 but \<10,000 or ≥10, 000
Incidence of patients with BK viremia stratified by the magnitude
时间窗: Throughout the study intervention up to 12 months post transplant
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.
次要结局
- Number of Participants Experiencing the Composite Outcome of Death or Allograft Failure(Up to 12 months post-transplantation, an average of 8 months)
- 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)
- Number of Participants Treated for Rejection(Up to 12 months post-transplantation, an average of 8 months)
- 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)
- Number of Participants With Biopsy-proven Active Antibody-mediated Rejection (BP-aABMR)(Up to 12 months post-transplantation, an average of 8 months)
- 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)
- 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)
- Number of Participants Who Develop De-novo Donor Specific Antibody (DSA)(Up to 12 months post-transplantation, an average of 8 months)
- Estimated Glomerular Filtration Rate (eGFR)(Baseline and 12 months post-transplantation)
- 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)
- Change in estimated GFR (eGFR)(Baseline and 12 months post transplantation)
- Number of subjects with biopsy-proven acute T-cell mediated cellular rejection (BP-aTCMR)(Up to 12 months post transplantation)
- Number of subjects 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)
- Number of subjects with biopsy-proven active antibody-mediated rejection (BP-aABMR)(Up to 12 months post transplantation)
- Number of subjects who develop de-novo donor specific antibody (DSA)(Up to 12 months post transplantation)
- Number of days to events [TCMR, ABMR, de-novo specific antibodies (DSA) formation, graft loss].(Up to 12 months post transplantation)
- The proportion of subjects experiencing the composite outcome of death or allograft failure(Up to 12 months post transplant)
- Number of subjects treated for rejection(Up to 12 months post transplantation)
- Number of subjects with changes in allograft biopsies for the 5 categories of aTCMR specified in the Banff schema(Up to 12 months post transplantation)
- Time to changes in allograft biopsies for the 5 categories of aTCMR specified in the Banff schema(Up to 12 months post transplantation)
研究者
Idelberto Badell
Assistant Professor
Emory University