Systemic Sclerosis (Scleroderma)

Researchers are studying pulmonary arterial hypertension PAH, including its common subtypes idiopathic PAH IPAH and connective tissue disease-associated PAH PAH-CTD. The study aims to develop pulmonary vascular biomarker signatures using hyperpolarized 129Xe MRI to differentiate these subtypes and to evaluate the ability of this imaging to monitor disease progression and treatment response over time. Additional assessments such as laboratory tests, echocardiography, and six-minute walk distance 6MWD are also used to support these evaluations. The study is observational and enrolls 20 subjects divided into two groups 10 with IPAH and 10 with PAH-CTD. Participants will undergo hyperpolarized 129Xe MRI and MR spectroscopy at baseline, 3 months, 6 months, and 12 months. Alongside imaging, data from standard clinical assessments including labs, echocardiography, and 6MWD will be collected at these same timepoints to track changes. Participants will be monitored for changes in pulmonary vascular remodeling, red blood cell oscillation amplitude, 6MWD, NTproBNP levels, and WHO functional class over one year. Safety is assessed by tracking adverse events, serious adverse events, withdrawals, and specific examinations such as electrocardiograms and vital signs. The total follow-up period for each participant is one year, with multiple scheduled evaluations to comprehensively assess disease status and response.

Researchers are investigating the specific targets of T cells involved in autoimmune diseases by studying tissues from patients with active organ inflammation caused by autoimmune conditions. The study aims to identify which T cells are activated and expanding in diseased tissues compared to blood or normal tissues. This information will help discover new peptide targets and their associated T cell receptors TCRs to develop potential new therapies for autoimmune diseases. Participants will provide tissue samples and matched blood samples during clinical procedures such as endoscopy, arthrocentesis, lumbar puncture, skin biopsy, bronchoscopy, or surgery, depending on their autoimmune condition. The study includes several groups covering diseases like Crohns disease, ulcerative colitis, celiac disease, ankylosing spondylitis, multiple sclerosis, scleroderma, systemic sclerosis, and other autoimmune diseases. Samples may come from excess clinical materials or research-specific biopsies, with the possibility of serial sampling over time. During the study, participants will undergo standard clinical procedures with collection of additional tissue or fluid samples and companion blood draws. Researchers will analyze these samples to identify peptide targets linked to disease-reactive T cells over a period of up to three years. The study includes comprehensive assessments of tissues and blood to understand T cell activity in autoimmune disorders, with monitoring of participant safety and no interventions beyond routine clinical care.

Researchers are evaluating an open-label, dose escalation study for patients with relapsed and refractory autoimmune diseases. The study focuses on a therapeutic biological product called TI-0032-III injection, which uses lipid nanoparticles to deliver circular RNA encoding the CD19 chimeric antigen receptor CAR targeting T cells. This treatment is intended for various difficult-to-treat B cell-related autoimmune diseases, including systemic lupus erythematosus, Sjgrens syndrome, systemic sclerosis, idiopathic inflammatory myositis, and antiphospholipid syndrome. Participants will receive multiple doses of TI-0032-III injection infused into the body. This in vivo CD19-targeted CAR T cell therapy is being studied for safety and efficacy, with treatment delivered over a period involving dose escalation. The trial is an interventional Phase 1 study where the investigational injection is the main intervention. During the study, participants will be monitored for safety outcomes from the first dose up to 12 months. Researchers will also assess efficacy outcomes for the different autoimmune diseases up to 3 months after the first dose. Evaluations include clinical assessments and laboratory tests to measure treatment impact and safety. The total participant involvement will span at least one year to observe safety and disease response.

Researchers are studying the safety and effectiveness of YTS109 cells in adults aged 18 to 65 with relapsed or refractory autoimmune diseases, including Systemic Lupus Erythematosus SLE and related conditions such as Lupus Nephritis LN, SLE-associated immune thrombocytopenia, Sjogrens Syndrome, systemic sclerosis, inflammatory myopathy, ANCA-associated vasculitis, and antiphospholipid syndrome. This phase 1, open-label study aims mainly to evaluate safety and also to examine how well YTS109 cells work and behave in the body. Participants will receive a single infusion of YTS109 cells, starting at a dose of 310 STAR-T cells per kilogram of body weight. The dosing will follow a 33 escalation design to carefully adjust the dose. There is only one treatment group in this study. The infusion is a one-time procedure during the treatment period. During the study, participants will be closely monitored through regular assessments up to 52 weeks after treatment. Safety is tracked by observing adverse events and their severity. Effectiveness is assessed at multiple time points from 2 to 52 weeks. Blood tests will measure YTS109 cell levels, cytokine changes, and B cell recovery. Participants must agree to informed consent and follow-up visits to complete all evaluations throughout the study duration.

Researchers are evaluating the safety and potential effectiveness of YTS109 cells in adults aged 18 to 65 who have relapsed or refractory autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, and several others. This exploratory clinical trial aims to better understand how well YTS109 cells work and their safety when used with a lymphodepletion regimen. The study is conducted as a single-arm, open-label trial at a single center. Participants will receive one infusion of YTS109 cells at a dose of 1.5 million cells per kilogram of body weight. The study focuses on monitoring adverse events and assessing efficacy over various time points. The treatment is designed to target and reduce B cells to help manage autoimmune responses. The trial plans to enroll approximately 6 to 12 patients. During the study, participants will be closely monitored for safety and treatment effects at intervals including 2, 4, 8, 12, 24, and up to 52 weeks after treatment. Researchers will conduct blood tests to measure the levels of YTS109 cells, biomarker changes, and immune system responses. The primary outcomes are the type, severity, and frequency of any adverse effects, along with efficacy evaluations. The total observation period extends up to one year to thoroughly assess safety and response to treatment.

Researchers are evaluating the efficacy, safety, and tolerability of subcutaneous ianalumab in adults with diffuse cutaneous systemic sclerosis, a condition characterized by skin thickening and other systemic symptoms. This Phase 2 study compares ianalumab to a placebo to understand its impact on this disease, aiming to provide new treatment options for affected individuals. The study is sponsored by Novartis Pharmaceuticals and employs a randomized, double-blind design to ensure reliable results. Participants receive either ianalumab or placebo through subcutaneous injections during the initial 52-week treatment period. After this, all participants enter a second 52-week open-label phase where they receive ianalumab. Following treatment, there is a post-treatment follow-up lasting at least 20 weeks and up to 2 years to monitor long-term effects. The study includes a screening period lasting up to 6 weeks before treatment begins. Throughout the study, participants undergo regular assessments including measuring response based on the rCRISS25 scale at Week 52, lung function tests, skin scoring, and disability index evaluations. Blood samples are taken periodically to measure drug levels and antibodies. Safety is closely monitored through adverse event reporting up to Week 208. The total participation time can extend over several years including treatment and follow-up phases.

This research focuses on people who have previously been treated with KYV-101, an autologous CAR T cell therapy, to monitor long-term safety and persistence of the treatment. It aims to collect information about delayed side effects and ongoing presence of the gene-modified cells in participants who received at least one infusion of KYV-101 in earlier clinical trials sponsored by Kyverna Therapeutics. Participants in this observational study will continue to be followed for up to 15 years after their initial KYV-101 treatment. The study will track various health outcomes including treatment-related adverse events, new or returning malignancies, neurological and autoimmune conditions, blood disorders, infections, and specific laboratory tests related to the therapy. For some participants with certain conditions, additional measures like medication use and functional assessments will be monitored for shorter periods. Throughout the study, participants will undergo regular health evaluations, lab tests, and questionnaires to assess the long-term effects of KYV-101. Researchers will collect data on safety events and laboratory markers up to 15 years, with some specific tests monitored up to 5 years. The overall goal is to better understand the long-term impact and safety profile of the gene-modified therapy in people treated previously.

Researchers are studying XmAb657 to evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity in healthy adults and adults with autoimmune diseases such as idiopathic inflammatory myopathies, systemic sclerosis, and Sjogrens disease. This Phase 1, first-in-human study aims to understand how the drug behaves in the body and its potential effects. Participants will receive XmAb657 by subcutaneous injection under the skin in a dose-escalation design. The study includes both healthy volunteers and individuals diagnosed with specific autoimmune diseases. The treatment phase involves administering XmAb657 and monitoring responses over time. During the study, participants will undergo various assessments including safety monitoring for treatment-emergent and serious adverse events, blood tests to measure drug concentration, and evaluations of pharmacodynamic effects. Researchers will track these outcomes through Week 52. Participants are expected to follow contraception requirements and attend scheduled visits for monitoring throughout the study duration.

Researchers are evaluating FT819, an investigational drug, in a phase 1 study for people aged 12 to 70 with moderate-to-severe active B-cell mediated autoimmune diseases. These conditions include 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 aims to assess the safety, how the drug is processed in the body, and its effect on B cells. The trial is sponsored by Fate Therapeutics and includes a dose-escalation stage followed by an expansion stage to further evaluate safety and activity. Participants will receive FT819 through intravenous IV infusion at planned dose levels. The study includes several treatment regimens, some using FT819 with an auxiliary medicinal product AMP and some without, combined with background therapies or temporarily suspending them. Other drugs such as fludarabine, cyclophosphamide, and bendamustine may also be administered as IV infusions at planned dose levels. The trial is non-randomized and open-label, with different dosing schedules including single or two-dose regimens. Participants will be closely monitored for treatment-emergent adverse events and dose-limiting toxicities up to approximately two years. Researchers will measure the plasma concentration of FT819, disease activity, and quality of life at designated time points. Safety assessments and evaluations of disease activity, including lupus nephritis when applicable, will be conducted throughout the study. The total participation time may extend up to two years to gather comprehensive safety and activity data.

Researchers are studying NKX019, an investigational allogeneic CD19-directed CAR NK cell therapy, to evaluate its safety and tolerability in adults with various autoimmune diseases. This Phase 12, open-label, multi-center study uses a dose escalation and expansion design to find recommended doses and assess preliminary effects including pharmacokinetics, pharmacodynamics, and immunogenicity. Participants will undergo a treatment cycle starting with lymphodepletion using fludarabine and cyclophosphamide before receiving three doses of NKX019. A modified lymphodepletion regimen using cyclophosphamide alone may be given to participants with low blood cell counts. The study includes dose escalation using a 33 design and subsequent enrollment of more participants at the recommended dose levels. During the study, participants will be closely monitored for side effects, treatment-related toxicities, and immune responses. Researchers will collect data on lung disease, systemic sclerosis, inflammatory muscle diseases, vasculitis, and rheumatoid arthritis up to two years after NKX019 infusion. Safety assessments cover the first 28 days after dosing and continue through 30 days after the last treatment. Total participation duration may extend to two years to observe long-term effects.