Antibody Mediated Rejection

To evaluate the safety and tolerability of SG301 injection in patients with antibody-mediated rejection (AMR) after renal transplantation.

The goal of the global Phase 1/2 clinical trial is to evaluate whether CID-103, a novel anti-CD38 monoclonal antibody, is safe and effective in adults with with active and chronic active renal allograft antibody mediated rejection (ABMR). The main questions the study aims to answer are:• To evaluate the safety and tolerability of CID-103 in subjects with ABMR with different increasing doses of CID-103.• To evaluate clinical efficacy of CID-103 at an optimal dose in participants with active and chronic active ABMR following renal allograft transplant. The study will be done in two parts: Part A will test increasing doses of CID-103 to see how safe it is and how well people tolerate it. Researchers will also aim to find a safe dose range. Part B will enroll approximately 40 participants to see how well the medicine works and gather more safety and efficacy information. The goal is to find the optimal dose to use in future studies.CID-103 is given through an intravenous (IV) infusion. During the study, participants may receive treatment for up to 12 months, followed by a post-treatment safety follow-up period to check for ongoing safety and effectiveness. This study is an important step toward developing a new treatment for people living with ABMR. If CID-103 is found to be safe and effective, it could offer a new option for patients who do not respond well to current therapies.

This multicenter, prospective, single-arm exploratory study evaluates the efficacy and safety of a novel sequential regimen for chronic active antibody-mediated rejection (caABMR) in kidney transplant recipients: single-dose CD38 monoclonal antibody (1800 mg subcutaneous) induction to deplete plasma cells and NK cells, followed by long-term maintenance with azathioprine (replacing mycophenolate mofetil) plus standard triple immunosuppression (steroid + calcineurin inhibitor). The regimen aims to control DSA-driven injury, stabilize or improve graft function (primary: eGFR decline slope), reduce DSA, improve pathology (Banff 2022), and minimize infection/nephrotoxicity risks associated with intensified or prolonged biologic therapy. Twenty patients across 6 Chinese transplant centers will be enrolled. CD38 mAb, azathioprine, key monitoring tests (HLA antibody, pharmacogenomics, immune profiling) are provided free by the study team (\~40,000 RMB per patient). Ethics approved; informed consent obtained.

Patients who have immune mediated diseases commonly undergo plasma exchange (PLEX) procedures to remove pathological substances, typically believed to be antibodies. At our facility about 400 of these procedures are performed annually on 40-60 different patients. These procedures are considered within the standard of care for these patients and are covered by insurance. This study will not influence the treatment plan for subjects who participate in this study. The goal of the study is to collect and cryopreserve blood biospecimens (plasma, serum, PBMCs) for current and future studies. Any patient undergoing plasma exchange procedures will be eligible for the study. Patients or the legally authorized representative (LAR) will be consented for the study as soon as feasible after the are referred to DeGowin for plasma exchange. The immediate objective of the study is to examine antibody levels (IgG/IgM) and BAFF levels in the blood of these patients over the course of the plasma exchange treatments. Specimens and clinical data will be collected such that other immune factors that may regulate B cell survival, proliferation and antibody secretion can be studied. Another goal of the study is to isolate and cryopreserve PBMCs at different points during the patient's treatment. This would allow the study of immune cells that may mediate these diseases. The study will also follow pathological antibodies over time in these patients so biospecimens can be obtained even after the completion of their course of plasma exchange treatments. The collection of biospecimens and clinical information from these subjects will help us understand the impact of plasma exchange on both normal and pathological immune factors in a variety of patients undergoing these procedures.

The goal of this clinical trial is to evaluate the therapeutic effect of extracorporeal photopheresis in subclinical antibody-mediated rejection after lung transplantation.The main questions it aims to answer are: 1. Does ECP therapy result in a significant reduction in MFI (Mean Fluorescence Intensity) from the baseline MFI in clinically stable patients with persistent (\>6 months) dnDSAs (MFI\>1000)? 2. What is the impact of ECP therapy on the following outcomes in these patients: ACR, clinical AMR, CLAD, infections, drop-out rate, survival, adverse events? Participants will be randomized into two groups. Each group will include 40 patients. The control group will be observed and no active treatment will be administered. The treatment group will receive extracorporeal photopheresis. First, a two-day treatment cycle will be performed once every second week for the first two months. Then, a two-day treatment cycle will be performed once a month for 6 months. Researchers will compare the two groups regarding: MFI value, development of ACR, clinical AMR, CLAD, infections, survival, adverse events, immunophenotyping, miRNA expression profiling, cytokine expression, gene expression signature of PBMCs and proteomic characterization.