Clinical Research Directory

Treatment of Antibody-Mediated Rejection (ABMR) With CarBel

The purpose of this study is to evaluate the safety and efficacy of carfilzomib and belatacept, administered with steroids and maintenance immunosuppression, in kidney transplant recipients with donor-specific antibody (DSA)-associated graft injury. Participants will be followed for 52 weeks after starting investigational therapy, including protocol biopsies at 3 months and 12 months after start of investigational therapy. The study will also assess changes in immune cell responses, blood and urine biomarkers, and biopsy-based pathomic features associated with antibody-mediated graft injury.

A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation

The purpose of this open-label, randomized, active-comparator-controlled study is to determine the efficacy and safety of frexalimab subcutaneous administrations up to 5 years compared to tacrolimus capsules in adults undergoing kidney transplantation. Participants aged 18 to 70 years who have low-to-moderate immunologic risk of graft rejection and receive their first kidney transplant are eligible if they meet all inclusion and no exclusion criteria. Study details include: * The study and treatment duration will be up to approximately 5 years. * The number of visits will be approximately 38.

Observational Cohort Study Renal Transplantation University Hospitals Leuven

This observational cohort study aims to compile routinely collected clinical, histological and outcome data of kidney transplant recipients, to evaluate risk factors for post-transplant injury, phenotypes of injury, and impact on outcome of such injury, in order to provide clinicians more accurate, less biased and faster tools for diagnosis, clinical management and treatment decisions with regard to kidney transplant rejection.

Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study

Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression exposure but are also at risk of graft loss from rejection with under-immunosuppression. Biomarkers that predict both iRAEs and rejection and allow individualisation of immunosuppression exposure are lacking. While plasma viral DNA levels of Torque Teno Virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in incident KTRs within 1 year after transplant, its role for prevalent KTRs on stable immunosuppression is unclear. The investigators hypothesise that plasma TTV levels can predict iRAEs and rejection in KTRs on stable immunosuppression and propose a pilot study to pursue three specific aims: (1) To determine the TTV levels and its relationship with clinical factors affecting the 'net state of immunosuppression' in prevalent KTRs. (2) To analyse the prognostic value of TTV levels for iRAEs and rejection in prevalent KTRs. (3) To compare the prognostic performance of TTV levels to commonly available biomarkers and composite prognostic scores. The investigators seek pursue these aims by performing a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured, using the TTV R-GENE® kit, upon recruitment and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The study will provide data on the distribution of TTV levels in a prevalent cohort of KTRs and analyse its relationship with clinical factors and important clinical outcomes. If the study indicates that TTV may be predictive of iRAEs and rejection, the investigators aim to conduct further studies including interventional studies using TTV levels to guide immunosuppression. Ultimately, the investigators aim to use TTV as a biomarker to optimise long-term immunosuppression exposure, reduce the risk of iRAEs without increase in rejection, and improve long-term outcomes for KTRs.

The smartNTx Trial:Telemedical Management Versus Standard Aftercare in Kidney Transplant Recipients (KTR)

The smartNTx trial: Prospective, randomized controlled trial (RCT) to investigate additional interventional telemedical management versus standard aftercare in kidney transplant recipients (KTR). STUDY PURPOSE: To demonstrate that additional interventional telemedical management will lead to a higher chance for long-term graft survival, increase adherence, quality of life (QoL), and reduce complications and healthcare costs after kidney transplantation.

Belimumab to Mobilise Memory B-cells From Secondary Lymhoid Organs to Improve Memory B-cell HLA-specificity Profiling to Support Delisting for Transplant Access in Highly-sensitized

The goal of this clinical trial is to determine whether belimumab can improve detection of circulating HLA-specific memory B cells to support safer and more effective donor organ allocation in highly sensitized kidney transplant candidates. The main questions it aims to answer are: Does treatment with belimumab change the antigen specificity profile of circulating HLA-specific memory B cells compared to pre-treatment measurements? Does a delisting strategy that incorporates mobilized memory B cells improve the probability of donor organ allocation and reduce time to transplantation? Participants will: Receive a short course of belimumab treatment Provide blood samples before and during treatment to assess memory B-cell profiles Undergo evaluation for potential adjustment of unacceptable HLA specificities (delisting) based on test results Be followed for donor organ allocation and transplantation outcomes

Trifecta-Kidney cfDNA-MMDx Study

Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.

Screening for Subclinical Antibody Mediated Rejection and Efficacy of Belatacept in the Context of de Novo Donor Specific Antibody After Kidney Transplantation (BELA-M-R)

Antibody mediated rejection (ABMR) is a major cause of graft loss after kidney transplantation (KT) and is mainly associated with preformed anti-HLA donor specific antibodies (DSAs) (phenotype 1) or de novo DSAs (dnDSAs) (phenotype 2). Preexisting DSA-associated ABMR have superior graft survival compared with dnDSA-associated ABMR, which could partly be explained by the fact that patients with de novo DSA-associated ABMR have biopsy later, when graft dysfunction and/or proteinuria are already present. ABMR is a progressive process with an early stage called subclinical ABMR (sABMR), in which histological lesions are present in the kidney graft without clinical graft dysfunction. These early lesions are now well recognized as risk factors for transplant glomerulopathy and poor graft survival in phenotype 1 ABMR (ref 5). The impact of sABMR associated with dnDSA at any time post-transplant has been less studied and reported. Recently, a retrospective multicenter study was published, within the Spiesser Group that included 123 patients without graft dysfunction who underwent graft biopsy because of the presence of dnDSA (One Lambda, MFI \> 1000). Performing a kidney graft biopsy after dnDSA indentification without renal dysfunction leads to the diagnosis of active sABMR in 35 % of cases. Nevertheless, no effect of standard of care treatment in active sABMR was observed. Very recently, an expert consensus for the recommended treatment for ABMR after KT was published. It was conclude that the clear lack of evidence but a standard of care for ABMR was nevertheless defined. Therefore, the current proposal is to evaluate a new strategy for active sABMR, testing a conversion from calcineurin inhibitor (CNI) to belatacept associated with the recently recommended standard of care (SOC) compared to continuing CNI. Belatacept might help to manage nonadherence, decrease the toxicity of CNI on an endothelium already affected by microvascular inflammation, and reduce DSA titers. The monitoring of dnDSA after KT and an indication graft biopsy in case of appearance, even in the absence of graft dysfunction, is not part of a routine clinical practice in all KT centers. This strategy could be a valuable option, in order to begin treatment of ABMR before graft dysfunction occurs, and therefore to improve prognosis associated with phenotype 2 ABMR. Parajuli et al.4 suggested that early diagnosis and treatment of sABMR with SOC, using DSA monitoring may improve outcomes after KT, but this is a retrospective and no-randomized study. This study will be the first prospective randomized study in the context of de novo DSA. The objective is to evaluate a new combination of treatment for ABMR in the context of dnDSA with subclinical lesions and in the same time may help to determine the real incidence of sABMR in KT recipients with subclinical dnDSA. The use of belatacept in the context of sABMR to improve the non-adherence and to decrease the endothelial toxicity had never been evaluated in a prospective way.

Evaluating Urinary CXCL10 for Enhanced Detection of Acute Rejection in Kidney Transplant Patients With Low DD-CFDNA

Kidney transplant rejection remains a significant challenge to long-term graft survival. While histological biopsy continues to be the gold standard for diagnosing rejection, noninvasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) have gained traction for their ability to detect allograft injury. However, dd-cfDNA may lack sensitivity in certain clinical scenarios particularly in cases of localized immune activation leading to false negatives despite biopsy-confirmed rejection.

Using MSCs for Chronic Active Antibody Mediated Rejection

Mesenchymal stem cell (MSCs) therapy has already been studied in kidney transplant recipients (KTRs), and the available data showed that it is safe and well tolerated. The aim of this study was to evaluate the safety and efficacy of autologous MSCs in combination with standard therapy in KTRs with biopsy-proven chronic active antibody-mediated rejection (AMR). Patients with biopsy-proven chronic active AMR received treatment with autologous bone marrow-derived MSCs (3 × 106 cells/kg iv) after completion of standard therapy and were followed for up to 12 months. The primary endpoints were safety by assessment of adverse events. Secondary endpoints included assessment of kidney graft function, immunological and histological changes related to AMR activity and chronicity assessed by conventional microscopy and molecular transcripts. A total of 3 patients were enrolled in the study before it was terminated prematurely because of adverse events. We found that AMR did not improve in any of the patients after treatment with MSCs. In addition, serious adverse events were observed in one case when autologous MSCs therapy was administered in the late phase after kidney transplantation, which requires further elucidation.

Treatment of Chronic Active Antibody Mediated Rejection With Tocilizumab

Chronic active antibody mediated rejection (CAMR) is a therapeutic challenge in transplant recipients that does not respond well to conventional treatments for acute antibody mediated rejection (AMR). Annually, 5000 kidney transplants are lost in the United States due to CAMR. The two-year graft survival rate in CAMR is approximately 20%, highlighting the need for a more efficient therapy for CAMR and directly targeting donor specific antibody (DSA) producing cells and reducing CAMRThere is no established treatment for this problem. While many centers intensify and optimize the dosage of immunosuppressive drugs, treatments such as plasmapheresis, IVIG, and rituximab, although effective in treating AMR, have not been successful in reducing DSA or improving kidney graft survival in CAMR patients. Despite these treatments, two-year graft survival can increase up to 55%. The use of anti-plasma cell treatments like bortezomib has also yielded inconsistent results.

AIIM Trial: Personalized Medicine Approach to Kidney Allograft Function

The objective of the proposed study it to perform a pilot clinical trial both to establish feasibility of applying a computational, augmented intelligence based approach, Phenotypic Precision Medicine (PPM), to optimizing combination drug therapy and to gather preliminary data to support a larger fully powered multi-center clinical trial. The key rationale for this clinical selection is that we have the technical, biological, and medical expertise in this disease, a wealth of experience in the use of PPM in both in vitro and the clinical setting, and a robust and integrated transplant program with a well-functioning clinical trial infrastructure.

Long-Term Safety and Efficacy of Tegoprubart in Kidney Transplant Recipients

This study will evaluate the long term safety and efficacy of AT-1501 (tegoprubart) compared with tacrolimus in patients undergoing kidney transplantation.

Platelet Aggregation in the Diagnosis of Acute Graft Rejection

The study titled "Platelet Aggregation in the Diagnosis of Acute Graft Rejection" is a pilot observational study evaluating whether alterations in platelet function can serve as non-invasive markers of acute rejection in kidney transplant recipients. Platelet aggregation is assessed using optical aggregometry, flow-cytometric P-selectin (CD62-P) expression, and soluble P-selectin levels before kidney transplantation and at the time of protocol biopsies performed at 3 and 12 months after kidney transplantation. Patients with suspected graft dysfunction undergoing indication biopsy are also included. Platelet activation markers are correlated with histopathological findings, donor-specific antibodies, metabolic parameters, and clinical outcomes. The goal is to determine whether platelet activation profiles can identify acute cellular or antibody-mediated rejection and contribute to the development of a non-invasive diagnostic tool.

Long-Term Follow-Up of TX200-TR101 (STEADFAST Long Term)

This long-term follow-up study is being conducted to collect long-term (up to 15 years post-infusion) safety and tolerability data from subjects enrolled in studies evaluating TX200-TR101.

Validation of Genomic Immune-phenotyping Profiles to Predict Risk of Kidney Transplant Rejection

Global, non-randomized, observational study for the validation of Verici Dx genomic tests to predict risk of kidney clinical and subclinical acute rejection, and chronic allograft damage or interstitial fibrosis / tubular atrophy by correlating peripheral blood gene expression profiles with graft injury (e.g. cellular / antibody-mediated), rejection and death censored graft loss.

Validation of Donor-Derived Cell-Free DNA (Dd-cfDNA) for Kidney Transplant Monitoring

The goal of this observational study is to learn if the donor-derived cell-free DNA (dd-cfDNA) test can assess rejection in kidney transplant recipients. Participants will have blood and urine collected at their study visit. Researchers will compare results of the GraftAssureDx to rejection detected by standard-of-care graft biopsies.

PIONEER Trial (Post-Transplant Application of TruGraf and TRAC Molecular Panel in Renal Transplant Recipients)

This is an observational, prospective, multi-center trial designed to evaluate clinical outcomes in kidney transplant recipients undergoing TruGraf and TRAC monitoring. Approximately 15 U.S. sites

Australian Genomics Of Chronic Allograft Dysfunction Study

The goal of the Australian Genomics of Chronic Allograft Dysfunction (AUSCAD) study is a single centre (Westmead Hospital), prospective, observational study, which enrols patients at time of kidney (or kidney-transplant) transplant and tracks the post transplant course. The AUSCAD study aims to generate new knowledge and improve outcomes following kidney transplantation. The primary aim is to determine whether important outcomes (including chronic rejection and graft loss) are correlated with patterns of allograft reactivity, gene expression and susceptibility profiles.

CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk

This clinical trial investigates the transplantation of donor kidneys that have been genetically modified ex vivo using CRISPR-Cas9 genome editing to reduce immunogenicity and transplant rejection. Donor kidney grafts will have key human leukocyte antigen (HLA) genes disrupted - specifically, knockout of HLA class I heavy chains HLA-A and HLA-B, along with disabling HLA class II expression by targeting the CIITA gene (a master regulator of HLA-DR/DQ/DP). Approximately 90 adult end-stage renal disease patients will receive a CRISPR-edited donor kidney transplant. The primary objectives are to assess the safety and feasibility of this novel intervention, while secondary objectives evaluate the reduction in immune responses (immunogenicity), graft function, and the practicality of implementing ex vivo gene-edited organ transplantation in humans. By knocking out major donor HLA molecules, the trial aims to reduce T-cell and antibody-mediated recognition of the graft, potentially lowering rejection rates and reliance on high-dose immunosuppressants. Safety, including any off-target effects or unanticipated immune reactions, will be closely monitored, and transplant outcomes will be tracked for one year post-transplant.

Microbiome and Immunosuppression: The Mission Study

The purpose of this research is to study immunosuppression drugs, certain foods, and how they can change the microbiome (the natural microorganisms inside the body) of the individual taking the immunosuppressive medications. The study team wants to study how the microbiome affects how the body processes the transplant medication.

PROACT Pilot Trial

Kidney transplantation is considered the best option to treat end-stage kidney disease, but the recipient's immune system may respond with rejection to the transplanted organ, leading to permanent kidney damage and failure. The current standard for rejection monitoring in transplanted recipients is regular blood creatinine testing and kidney biopsies. Creatinine doesn't detect rejection until damages had occurred, causing some amount of kidney failure, and kidney biopsies are only done at set timepoints. A new test called CXCL10 is shown to be more effective in detecting rejection from previous research and can be done as often as needed. Therefore, The investigators are doing this randomized trial to test CXCL10 as part of clinical care and to help design a larger national clinical trial in the future.

Longitudinal Changes in Donor-Derived Cell-Free DNA With Tocilizumab Treatment for Chronic Antibody-Mediated Rejection

Our group recently reported that tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, may be effective when administered monthly to patients with chronic antibody-mediated rejection (ABMR). The current paradigm to assess response to therapy involves serial monitoring for donor-specific antibodies, measurement of kidney function with creatinine, and periodic kidney transplant biopsies to survey for histologic findings indicative of ongoing ABMR. A new non-invasive blood test, donor-derived cell-free DNA (Allosure) has recently reported to have a high degree of discrimination for rejection and may be used to assess the likelihood of rejection. It has not been tested to see if it can be used to assess treatment response for rejection. This study will assess longitudinal changes in donor-derived cell-free DNA measurements in response to monthly therapy with tocilizumab for chronic ABMR and correlate these measurements to histologic changes on a follow-up kidney transplant biopsy.

Impact of the Microbiota on the Likelihood of Renal Graft Rejection

Identification of a bacterial signature in the blood or stool that may be associated with acute rejection in patients treated with Nulojix during their first year of transplant.