ANCA-Associated Vasculitis (AAV)

This is the first-in-human trial of MTS109 (mRNA-LNP). The goal of this clinical trial is to evaluate the safety, tolerability of intravenous injection of MTS109 in moderate to severe autoimmune diseases.

The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel versus comparator in participants with severe active Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)

The primary aim is to study the efficacy of treatment with BDB-001 Injection to induce remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab

Safety, tolerability and efficacy of Descarte-08 in children, adolescents and young adults with childhood-onset systemic lupus erythematosus, ANCA-associated vasculitis, juvenile myasthenia gravis, and juvenile dermatomyositis

The PREP-ANCA study seeks to establish a more personalized treatment strategy for ANCA-associated vasculitides by assessing the efficacy of pre-emptive rituximab administration upon ANCA repositivity in preventing relapses in granulomatosis with polyangiitis and microscopic polyangiitis.

This exploratory, single-arm, open-label study will evaluate the safety and preliminary efficacy of YTS109 cell therapy in pediatric patients with relapsed/refractory autoimmune diseases, including systemic lupus erythematosus, diffuse systemic sclerosis, idiopathic inflammatory myopathies, and Sjögren's syndrome, as well as other eligible autoimmune diseases defined by the protocol eligibility criteria. Approximately 12 patients aged 5 to \<18 years will be enrolled at Children's Hospital of Fudan University and will receive a single intravenous infusion of YTS109 cells. Dose escalation will follow a standard 3+3 design starting at 1.5 × 10\^6 cells/kg. The primary objective is to assess the safety and preliminary efficacy of YTS109 cell therapy in this population. Secondary objectives include characterizing the pharmacokinetic and pharmacodynamic profiles of YTS109 cells. Primary endpoints include the type, severity, and frequency of adverse events, along with efficacy assessments.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune condition characterised by inflammation of small blood vessels. The condition causes multi-organ dysfunction and, if left untreated, is usually fatal. AAV is difficult to diagnose and the degree of disease activity is challenging to monitor. Current methods of disease activity assessment are either inaccurate (blood tests), invasive (biopsy), or non-specific (imaging). Additionally, though modern treatments are effective, patients with AAV remain at a substantially increased risk of cardiovascular disease (CVD) in the long-term. There is therefore an urgent need for a tool which is able to reliably identify disease, and assess long-term CVD risk. Total-Body PET imaging with FDG, DOTATATE, and FAPI radiotracers may provide the answer. This study will recruit patients with active AAV, together with a control group of individuals without the disease, to undergo Total-Body FDG, DOTATATE, and FAPI PET scanning and compare the results with established measures of disease activity and CVD risk assessment. The investigators believe that Total-Body PET scanning will be capable of accurately identifying AAV disease and those at increased CVD risk. This could enhance understanding and improve the management of those with the condition. This study will recruit a group of patients with AAV and a comparator groups of 'matched' individuals without AAV. Comparisons between groups will allow the investigators to ensure that the changes seen are due to AAV disease. The study will recruit a minimum of 30 and a maximum of 90 participants in the AAV group, and a minimum of 10 and maximum of 30 participants in the matched control group. AAV subjects and matched control subjects will undergo baseline total-body PET scanning with either one, two or three radiotracers (\[18F\]-FDG, \[68Ga\]-DOTATATE, and \[68Ga\]-FAPI). Alongside this they will receive assessment of cardiovascular disease risk including 24-hour blood pressure measurement, arterial stiffness measurement, and retinal scanning. Participants will also supply a blood and urine sample. For matched control subjects, their participation will end at this point. Subjects in the AAV group will undergo repeat assessment with total-body PET imaging and cardiovascular disease risk measurement once their condition is in remission (usually after around 3-6 months). The investigators will compare PET scan results between groups, and with cardiovascular assessments. This will allow determination of whether total-body PET scanning can identify AAV disease activity, and whether it can inform CVD risk. All research activity will be carried out within the University of Edinburgh BioQuarter, including the Royal infirmary of Edinburgh, the Edinburgh Imaging Facility, and Queen's Medical Research Institute.

This is an open clinical pharmacological translational Research Study, aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RD06-05 in patients with active SLE, SSc, AAV, IIM, NMOSD, MS, MG

ANCA-associated vasculitis (AAV) is a rare auto-immune disease, with high mortality in the absence of treatment. There is still an unmet need to define new treatment strategies to reduce drug side effects, as well as to reverse rare cases of refractory AAV and improve the kidney response to improve the long-term outcomes. Severe forms of AAV-related necrotizing and crescentic rapidly progressive glomerulonephritis (RPGN) (i.e. estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m²) are associated with higher mortality, higher incidence of infections, and long-term consequences including chronic kidney disease (CKD) with subsequent complications (end-stage kidney disease (ESKD) requiring dialysis, cardiovascular diseases) and a burden of financial costs. In patients with AAV and RPGN, recent guidelines recommend using a standard-of-care (SOC) immunosuppressive regimen including an induction regimen (rituximab or cyclophosphamide), plus glucocorticoids (GCs) (starting at 60 mg/day and tapering over 6-12 months) (+ or - plasma exchanges). Since GCs also participate to the long-term control of AAV, new molecular pathophysiology-driven therapeutic approaches rapidly blocking and/or reversing AAV lesions are needed to go beyond the progressive control of AAV using GCs alone. Thus, an add-on approach including GCs-based immunosuppressive regimen plus a new targeted therapy may lead to both AAV control (systemic disease) and improvement of the kidney outcome (organ involvement). Avacopan a selective inhibitor of the C5a receptor, recently emerged as a new therapeutic option in AAV. In a phase 3 comparative study (that included a small subset of patients with eGFR 15-29 mL/min/1.7m2), avacopan was superior to glucocorticoids taper with respect to sustained remission at week 52. In the avacopan arm, the cumulative dose of GCs was dramatically reduced and avacopan was thus proposed as an alternative to GCs rather to a synergic treatment. In the subgroup of patients with eGFR \<30 mL/min/1.73m², avacopan was associated with a better eGFR gain at week 52 compared to prednisone, but data in this population at-risk of worse kidney outcomes are scarce, and did not include patients with eGFR \< 15 mL/min/1.73m², those patients being excluded from the study. In the REVERSE study, investigators put forward the hypothesis that avacopan added on GCs regimen may significantly improve the kidney outcome of severe AAV (synergic approach), and thus improve short- and long-term global outcomes (survival, cardiovascular status). REVERSE will thus compare GCs-based SOC + placebo to GCs-based SOC + avacopan.

CAR T-cell Therapy Targeting CD19 and BCMA(QT-019C) in Patients With Relapse/Refractory Autoimmune Diseases

This study is a single-center, open-label, single-arm, dose-escalation trial. The aim of this study is to investigate the safety and efficacy of Anti-CD19 IL-10/IL15 CAR-NK cells in patients with refractory/relapsed autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myositis, ANCA associated vasculitis, sjogren syndrome, and antiphospholipid syndrome.

CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapse/Refractory Autoimmune Diseases

The CARe RAiSE project represents a pioneering translational initiative aimed at advancing precision medicine in the treatment of autoimmune rheumatic diseases. The primary objective is the development and implementation of an innovative cell-based ex vivo assay that enables individualized prediction of therapeutic response to disease-modifying antirheumatic drugs (DMARDs). By identifying the most effective treatment option for each patient, this approach seeks to enhance therapeutic efficacy, reduce time to clinical response, and minimize healthcare costs. Despite the availability of numerous DMARDs, clinical decision-making remains largely empirical due to considerable interindividual variability in treatment response. This frequently results in a prolonged trial-and-error process, placing a significant burden on patients and the healthcare system. CARe RAiSE aims to overcome this limitation by providing a functional diagnostic tool that can predict a patient's immunological response to specific DMARDs prior to treatment initiation. The assay is based on peripheral blood mononuclear cells (PBMCs) obtained from individual patients, enabling a physiologically relevant assessment of immune responsiveness to targeted therapies. Combining high-content imaging with homogeneous well-based cytokine and inflammasome activity assays, the platform allows for a detailed single-cell analysis of inflammatory pathways. These data are used to generate predictive signatures of treatment response, thereby facilitating a mechanistically informed and personalized therapeutic strategy. Through this approach, CARe RAiSE introduces a scientifically grounded, efficient, and patient-specific method for DMARD selection, with the potential to substantially improve patient outcomes and reduce the socioeconomic impact of autoimmune rheumatic diseases.

Autoimmune diseases refer to a common category of diseases caused by the immune system reacting to self-antigens, leading to tissue damage. Autoimmune diseases encompass a wide variety of conditions, such as systemic lupus erythematosus（SLE）, Sjögren's syndrome (SS), systemic sclerosis (SSc), inflammatory myopathies (IM), ANCA-associated vasculitis (AAV), and antiphospholipid syndrome (APS). They affect the quality of life, while in severe cases, they can be life-threatening. Additionally, they impose a heavy economic burden on society. Current treatments for autoimmune diseases include glucocorticoid, immunosuppressants, and biologics. B cell-driven humoral immune abnormalities are a central pathogenic mechanism in many autoimmune diseases. When autoreactive B cells are excessively activated, they produce large amounts of autoantibodies and immune complexes. These antibodies and immune complexes can cause damage to various tissues and organs, leading to the development of multiple autoimmune diseases. Therefore, targeting B cells to treat autoimmune diseases is an attractive therapeutic strategy. Chimeric Antigen Receptor (CAR)-T cells targeting the B cell surface molecule CD19 have achieved significant clinical progress in acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma, with several CD19 CAR-T therapies approved for marketing worldwide. Increasingly, clinical studies are exploring the use of CD19 CAR-T cells for the treatment of autoimmune diseases, and their therapeutic efficacy has been demonstrated. In this study, the investigators used γδ T cells as carrier cells to investigate the safety and efficacy of universal CAR-γδ T cells in the treatment of autoimmune diseases.

A clinical study exploring the safety, efficacy, and cellular metabolic kinetics of universal CD19/20 CAR-T cell injection in anti neutrophil cytoplasmic antibody associated vasculitis. This study is a single arm, open label, exploratory dose escalation clinical trial aimed at evaluating the safety, efficacy, and cellular metabolic dynamics of CT1192 cells in patients with ANCA associated vasculitis.

The goal of this clinical trial is to investigate the effect of the glifozines on albuminuria in chronic kidney disease patients affected by lupus nephritis and ANCA associated renal vasculitis. It will also learn about the safety of glifozines. The main questions it aims to answer are: * Does glifozines lower the albuminuria of participants with chronic kidney disease secondary to lupus nephritis and ANCA associated renal vasculitis? * What medical problems do participants have when taking glifozines? Participants will: * Take glifozines every day for 6 months. * Baseline, 1 month and 6-month visits will be scheduled to collect demographic, clinical, biochemical, and urinary data. * A psychosocial assessment will be performed.

This study aims to characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of OL-108 in relapsed/refractory autoimmune diseases.

The goal of this clinical trial is to learn if avacopan in combination with short-term (4 weeks) reduced-dose glucocorticoid and rituximab works to treat patients with newly-onset ANCA-associated vasculitis. It will also learn about the long-term safety of avacopan. The main questions it aims to answer are: Is avacopan in combination with short-term reduced-dose glucocorticoid and rituximab as effective as the combination of 20 week reduced-dose glucocorticoid and rituximab in the proportion of the patients achieving remission? Does avacopan lower the relapse rate compared to the 6 monthly rituximab maintenance therapy? What medical problems do participants have when taking long-term avacopan? Participants will: Be treated with avacopan in combination with short-term (until 4 weeks) reduced-dose glucocorticoid and rituximab (at 0 week) or reduced-dose glucocorticoid (until 20 weeks) and rituximab (at 0, 26, 52 and 78 weeks). Be assessed at 0, 4, 8, 16, 26, 52, 78 and 104 weeks regarding disease status (remission/relapse), disease activity by Birmingham Vasculitis Activity Score ver3, disease damage by Vasculitis Damage Index and adverse events. The primary endpoint is remission rates at 26 weeks.

The AYLo study (AutoimmunitY and Loss of y - Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases) aims to systematically investigate hematopoietic mutations, such as hematopoietic (mosaic) loss of the Y chromosome (mLOY), focusing on their underlying causes, pathophysiological significance, patterns of manifestation, and impact on disease progression in autoimmune, rheumatologic disorders. This research seeks to bridge existing knowledge gaps by exploring how such mutations influence immune homeostasis, cellular function, and susceptibility to inflammation-driven pathologies. Through the integration of advanced immunological profiling, the study aspires to uncover key mechanisms that drive the initiation, progression, and complications of autoimmune rheumatic diseases. These analyses will combine single nucleotide polymorphisms (SNP) arrays, multiplex assays, transcriptomics, and flow cytometry staining of peripheral blood mononuclear cells to delineate the interplay between hematopoietic mutations and immune dysregulation. A further objective is the development of a multimodal framework for disease-specific characterization, enabling precise mapping of mutation-driven phenotypes across diverse autoimmune conditions. This framework will incorporate clinical, molecular, and imaging data. Additionally, the AYLo study aims to explore the potential role of mLOY and other hematopoietic mutations as biomarkers for disease stratification, prognosis, and therapeutic response. The findings may open avenues for personalized treatment approaches, leveraging the molecular insights to inform targeted interventions and improve patient outcomes in autoimmune rheumatic disorders. By integrating translational and basic science approaches, this study has the potential to redefine current paradigms in autoimmune disease research and therapy.

Autoimmune diseases refer to a common category of diseases caused by the immune system reacting to self-antigens, leading to tissue damage. Autoimmune diseases encompass a wide variety of conditions, such as systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, inflammatory myopathies, ANCA-associated vasculitis. Current treatments for autoimmune diseases include glucocorticoid, immunosuppressants, and biologics. B cell-driven humoral immune abnormalities are a central pathogenic mechanism in many autoimmune diseases. When autoreactive B cells are excessively activated, they produce large amounts of autoantibodies and immune complexes. These antibodies and immune complexes can cause damage to various tissues and organs, leading to the development of multiple autoimmune diseases. Therefore, targeting B cells to treat autoimmune diseases is an attractive therapeutic strategy. Clinical studies are exploring the use of CD19-targeting CAR-T cells for the treatment of autoimmune diseases, and their therapeutic efficacy has been demonstrated. In this study, we investigate the safety and efficacy of universal CD19-targeting CAR T cells in the treatment of autoimmune diseases.

The rare autoimmune rheumatic diseases (RAIRDs) are life-long multi-system diseases that are life or organ threatening. RAIRDs can impair quality of life similar to chronic diseases such as heart failure. The aim of the study is to explore content and structure of a support programme for people with RAIRDs in focus groups and survey meetings.