Systemic Sclerosis (SSc)

This research will evaluate the effect of diets on bloating/distention, assess changes in abdominal pain, and overall gastrointestinal symptom burden in Systemic Sclerosis. The researchers will do this by comparing outcomes of people assigned to 3 different diets. Following the research specifics of the diets will be available upon contact with the details listed below.

This study is a Phase 1/2, open-label clinical trial to test an experimental treatment called QEL-005 in adults with two autoimmune conditions: diffuse cutaneous systemic sclerosis (dcSSc) and difficult-to-treat rheumatoid arthritis (D2TRA). The main goals are to find out whether QEL-005 is safe, how well people tolerate it, and whether it may help reduce disease activity or improve symptoms. QEL-005 is made from a participant's own white blood cells (autologous cells). These cells are collected and then changed in a laboratory using genetic methods to create specialized immune cells called CAR-T regulatory cells that target a protein on B cells called CD19. These modified cells are then given back to the participant by intravenous (IV) infusion. To take part, eligible participants will first have a procedure called leukapheresis, where some of their white blood cells are removed from the blood. The study team will use these cells to manufacture QEL005. After QEL005 is ready, participants will receive an IV infusion of their modified cells, stay in hospital overnight for monitoring, and will then be followed closely in the clinic. Throughout the trial, participants will have regular safety checks, which may include blood tests, imaging scans, questionnaires about symptoms and daily functioning, and biopsies taken from involved tissues, to help understand how QEL005 is working in the body. Detailed follow up will be for 1 year after QEL-005 infusion, and there is long-term follow up for a total of 15 years, which is standard for cell therapies. The information from this Phase 1/2 study will help determine an appropriate dose and dosing schedule of QEL005 for future studies.

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.

A two-part study of PRO-203 administered subcutaneously in healthy adult volunteers and participants with Systemic Sclerosis (SSc).

The objective of the study is to establish an in vitro model using iPSCs to test the hypotheses developed. The primary objective is to generate, via the SAFE-IPS platform, 8 iPSC lines derived from blood samples taken from: * Two patients with severe/diffuse SSc with multi-organ involvement (with anti-SCl-70 autoantibodies) * Two of their healthy close relatives * Two patients with uncomplicated SSc with localized involvement (with non-SCl-70 autoantibodies) * Two of their healthy close relatives These 8 cell lines will be differentiated by several teams at the FHU REGENHAB into: * Immune cells (monocytes/macrophages, neutrophils, dendritic cells, B/T lymphocytes) * Mesenchymal stromal cells * Myocardial cells * Skin cells (fibroblasts) * Synovial cells * Bronchial cells * Endothelial cells This project aims to map cellular and tissue heterogeneity using iPSC lines obtained from patients with both severe and mild SSc, employing single-cell RNA-seq under various pathological conditions, with and without autologous (or even heterologous) autoimmune stimulation. For example, the percentages of different cell types comprising a tissue in these various situations will be calculated. Comparisons will be made with control groups using healthy iPSC lines by recruiting healthy subjects with the same genetic profile and gender as the patients.

AID is a phase I multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (SLE-Non renal, SLE-LN, SSc/dcSSc) after receiving standard therapy.

Systemic Sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by microvascular injury, immune activation, and progressive fibrosis of the skin and internal organs. Diffuse cutaneous SSc (dcSSc), particularly in its early phase, is associated with aggressive fibrotic evolution and high morbidity. Despite advances in immunomodulatory therapy, no treatment has proven capable of consistently halting or reversing fibrosis, highlighting the need for new mechanistic targets. TL1A (TNF-like ligand 1A) is a cytokine of the TNF superfamily expressed by endothelial and immune cells, which interacts with death receptor 3 (DR3) to regulate immune activation, endothelial dysfunction, and tissue remodeling. Elevated TL1A levels have been observed in SSc patients and correlate with disease activity. TL1A has also been shown to promote lung fibrosis in preclinical models. The FIBROSTOP study is a proof-of-concept, in vitro, interventional study on biological samples aimed at elucidating the immunological and fibrotic mechanisms regulated by TL1A, and at assessing whether TL1A inhibition can reverse pathogenic processes in SSc. Ten (n=10) patients with early diffuse cutaneous SSc and ten (n=10) age- and sex-matched healthy controls will be enrolled at a single center (Fondazione Policlinico Universitario Campus Bio-Medico, Rome). Each participant will undergo a single visit (T0) involving peripheral blood sampling and skin biopsy. No follow-up visits are planned. The study pursues three co-primary objectives: (1) evaluating the role of TL1A and its inhibition in modulating T lymphocyte activity; (2) assessing the effects of TL1A and its inhibition on endothelial cell activation and function; (3) investigating the impact of TL1A and its inhibition on fibrotic remodeling in ex vivo SSc skin cultures using single-cell RNA sequencing. The findings may inform future targeted antifibrotic interventions in SSc and other fibrotic diseases.

A Basket Trial of Refractory Rheumatoid Arthritis (RA), Sjögren's Disease (SjD), Idiopathic Inflammatory Myopathies (IIMs) and Systemic Sclerosis (SSc) subjects to evaluate the safety and efficacy of AlloNK, a non-genetically modified allogeneic NK cell, in combination with rituximab.

This is a phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and anti-B-cell activity of FT819 following treatment with or without auxiliary medicinal product (AMP) in participants with moderate-to-severe active systemic lupus erythematosus (SLE) with or without nephritis, antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). The study will consist of a dose-escalation stage, followed by an expansion stage to further evaluate the safety and activity of FT819.

This is an exploratory, open-label, single-arm clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219CX. QT-219CX is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219CX .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .

The specific objective of this study is to perform a small, open-label study to assess the safety and efficacy of intralesional, subcutaneous injection of STS on calcinosis symptoms and lesion size in systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and dermatomyositis (DM) patients. Injection will be guided by ultrasound, lesion size assessed by ultrasound, and symptom burden by patient-reported outcome measures.

A Phase 1 study of HBI0101 BCMA-CART in B-Cell Mediated Autoimmune Rheumatic Diseases. The goal of the study is evaluation of safety and identification of the maximum HBI0101 CART dose that may be administered safely to patients with B-cell mediated autoimmune disease.

The main purpose of this study is to evaluate the effect and safety of efgartigimod PH20 SC compared to placebo in adults with systemic sclerosis. The study consists of a screening period, a treatment period of up to 48 weeks and a safety follow-up period. After the screening period, eligible participants will be randomized in a 2:1 ratio to receive either efgartigimod PH20 SC or placebo. The total study duration can be up to approximately 15 months. More information can be found on: https://clinicaltrials.argenx.com/esscape

The goal of this clinical trial is to evaluate the safety and tolerability of human umbilical cord mesenchymal stem cell injection(HS\_SW01 Cells injection) in patients with systemic sclerosis, and to further explore its pharmacokinetics(PK), immunological profile and preliminary efficacy. Participants will be required to sign the informed consent form and will only be assigned to the study and enrolled after undergoing a series of tests and meeting the inclusion and exclusion criteria of the protocol.

This is an open-label, single-dose, prospective, monocenter, Phase I interventional study (not first-in-human) to assess the safety, tolerability, and preliminary efficacy of autologous anti-CD19 CAR-T cells as an advanced therapy medicinal product in adult patients; with severe and refractory systemic autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's disease (SjD), systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM).

The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 12 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no immunosuppression, as well as in healthy volunteers matched by sex and age. The main questions it aims to answer are: Does the vaccine induce adequate seroconversion in patients with ARDs compared to healthy controls? What is the frequency and intensity of common adverse events after vaccination in ARDs patients? Does physical activity levels and nutritional status influence vaccine-induced immune response in patients with ARDs? Researchers will compare patients with ARDs to healthy controls to evaluate if the vaccine elicits similar immune responses and safety profiles. All participants will: * receive a single 0.5 mL dose of the Butantan-DV vaccine via subcutaneous injection; * undergo blood sample collection before and after vaccination (baseline, Day 42, and Day 400) to assess antibody and cellular responses; * attend follow-up visits on Days 7, 14, and 42 for safety monitoring and laboratory tests; * report any symptoms or adverse events using a standardized diary for 42 days; * be followed for up to one year for long-term safety and immunogenicity assessments. * wear a device for 14 consecutive days to assess current and habitual physical activity levels. * answer three non-consecutive 24-hour dietary recalls, including at least one weekend day to assess nutritional status. * collect blood samples one-year after vaccination to access immunogenicity and cellular response. Researcher will also perform subgroups analysis in: A viremia subgroup (50 patients and 50 healthy controls) will provide additional samples on Days 1, 7, 14, 28, 42, and-if viremia is detected-Day 68, to evaluate post-vaccination viremia and its duration. An immunogenicity subgroup (\~20% of participants, n=96) will undergo cellular immune response testing via flow cytometry to evaluate T-cell responses.

This is an open-label, single-arm study designed to evaluate the safety and preliminary efficacy of HN2302 in patients with autoimmune diseases, including systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).

This is an exploratory, open-label, single-arm Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219C. QT-219C is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219C .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .

A Clinical Study Exploring CT1190B in the treatment of patients with moderate to severe refractory systemic lupus erythematosus (SLE) or refractory/progressive systemic sclerosis (SSc)

This study evaluates the safety and efficacy of YTS109 cells in adults with relapsed/refractory autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), including LN and SLE-ITP, Sjogren's Syndrome, etc. Aproximately 18 patients aged 18-65 will receive a single infusion of YTS109 cells. The dose groups are set to commence at 3×10⁶ STAR -T cells/kg, employing a 3+3 escalation principle for dose titration. The primary objective of this study is to evaluate the safety of YTS109 cells therapy in treating recurrent/refractory autoimmune diseases, while the secondary objectives are to assess the efficacy of YTS109 cells as well as their pharmacokinetic and pharmacodynamic characteristics. The primary endpoint is observations of types, severity, and frequency of adverse events (AEs) and efficacy assessment. This single-arm, open-label trial will enroll patients across The First Affiliated Hospital of Anhui Medical University.

The main purpose of this study is to develop sensitive radiographic measurement techniques that can be used as outcome measures along with patient-reported outcome instruments in clinical trials of calcinosis cutis treatments, and potentially be used to assess disease course and treatment response in clinical practice. The goal is to test the performance of the software.

The study is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of tibulizumab over 24 weeks (Period 1) in adult participants with systemic sclerosis, followed by an open-label extension period where all active participants will receive tibulizumab and will be evaluated for an additional 28 weeks (Period 2)

This is an open-label, dose escalation study in patients with relapsed and refractory autoimmune diseases. Study drug, TI-0032-III injection, is composed of lipid nanoparticles (LNPs) targeting T cells that encapsulate circular RNA encoding the CD19 chimeric antigen receptor (CAR), which is a therapeutic biological product. It is clinically intended for the treatment of various relapsed and refractory B cell-related autoimmune diseases, such as systemic lupus erythematosus, sjögren's syndrome, systemic sclerosis, idiopathic inflammatory myositis, and antiphospholipid syndrome.

The purpose of this long-term follow-up (LTFU) study is to collect delayed adverse events (AEs) and understand the persistence of KYV-101 (autologous CAR T cell product; gene-modified product), in participants who have been administered KYV-101 (gene-modified product; autologous CAR T cell product). This LTFU protocol will be open to any participant who received at least one infusion of KYV-101 in a previous Kyverna sponsored clinical trial or Investigator Initiated Trial (IIT).

This study aims to measure a blood protein called fibroblast activation protein (FAP), which is linked to tissue scarring and inflammation. A small blood sample will be taken from participants (RA , SSc patients and healthy people ), and the FAP level will be measured and compared with routine clinical examinations, imaging studies, and lung function tests. The purpose of this study is to improve understanding of disease activity and lung involvement in these conditions and to explore whether FAP could be useful as a blood marker for future patients. Participation in this study will not change the participant's usual medical care.