Mixed Connective Tissue Disease

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.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

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 evaluating the safety, tolerability, pharmacokinetics PK, and pharmacodynamics PD of GenSci136 in healthy adult volunteers. This randomized, double-blind, placebo-controlled Phase 1 trial aims to study a single subcutaneous injection of GenSci136. The study focuses on how the drug behaves in the body and its effects, while monitoring for any adverse reactions over time. Participants will receive single ascending doses of GenSci136 or a placebo administered under the skin. The study is designed with dose escalation to evaluate different amounts of the drug. Both the experimental drug and placebo are given through subcutaneous injections in a controlled setting. During the study, participants will be closely observed from Day 1 through Day 113. Researchers will monitor for treatment-emergent adverse events and serious adverse events to assess safety. Blood samples will be collected to measure drug concentration, its maximum level, time to reach maximum level, elimination half-life, and other pharmacokinetic parameters. In addition, changes in specific biomarkers related to immune response will be measured. The trial involves regular visits and assessments over approximately 16 weeks to ensure thorough monitoring and data collection.

Researchers are studying the natural progression of Interstitial Lung Disease ILD and related conditions such as Idiopathic Pulmonary Fibrosis, Sarcoidosis, and Connective Tissue Disorder. The goal is to collect detailed data and blood samples from patients receiving care in the ILD program as well as from a control group to better understand the different ways these diseases can appear and progress over time. Participants in this observational study will not receive a specific treatment but will contribute data and blood samples over time. This approach allows researchers to compare disease characteristics in affected patients with those in healthy controls, aiming to describe the phenotypic expression of these lung diseases. Throughout the study, participants will have yearly evaluations to track the natural history of their lung disease. Data collection will include clinical assessments and blood samples to monitor disease progression. The study is ongoing, with participation potentially lasting for many years, allowing for long-term observation of the disease course.

Researchers are evaluating the long-term safety and effects of belimumab in adults with interstitial lung disease ILD linked to systemic sclerosis SSc and other connective tissue diseases CTD. This open-label extension study builds on previous randomized controlled trials to see if belimumab can continue to slow lung function decline, disease progression, and improve quality of life in these patients. Participants in this study will receive belimumab as the investigational treatment. The study continues from prior trials, focusing on long-term use and tolerance. Participants will be monitored over time to assess how well belimumab is tolerated and its impact on lung function and overall disease status. During the study, researchers will track adverse events, including serious and special interest events, for up to approximately five years. They will also measure changes in lung function using forced vital capacity FVC at multiple time points baseline, 12, 26, and 52 weeks. Participants will undergo regular assessments to monitor safety, disease progression, and quality of life throughout the study period.

Researchers are studying how the medicine dazukibart works in people with active idiopathic inflammatory myopathies, specifically dermatomyositis DM or polymyositis PM. These conditions cause inflammation and weakness in muscles near the bodys center, affecting activities like climbing stairs or lifting objects. DM also involves a skin rash, and these disorders can impact lung and heart function, reducing quality of life. This trial is designed as a Phase 3, multi-center, open-label extension to assess long-term safety, tolerability, and effects of dazukibart. Participants who took part in a prior dazukibart study and completed up to Week 52 may join this extension. Those receiving dazukibart will get an intravenous IV infusion lasting about one hour every 4 weeks for up to 48 weeks about 12 months. After the treatment period, there is a safety follow-up lasting about 4 months. Participants who choose not to receive the study medicine or are ineligible will only participate in safety follow-up visits, which happen every 4 weeks for up to 4 visits. During the study, participants receiving dazukibart will attend about 18 visits over roughly 16 months, while those on safety follow-up alone will have up to 4 visits. The trial monitors treatment-emergent side effects, lab and vital sign changes, lung function Forced Vital Capacity and lung gas exchange, and mental health using the Columbia-Suicide Severity Rating Scale. Secondary measures include muscle strength, disease activity assessments, patient-reported physical function, fatigue, quality of life, and medication use. This comprehensive monitoring helps evaluate the long-term impact of dazukibart in managing idiopathic inflammatory myopathies.

Connective tissue disease CTD is an autoimmune and inflammatory condition often linked with lung inflammation and scarring called interstitial lung disease ILD. The number of people affected and deaths from CTD-ILD have increased recently. While corticosteroids and strong immunosuppressants help some patients, progressive lung fibrosis can lead to respiratory failure and may require lung transplantation. Stem cell therapy is emerging as a new approach for treating CTD-ILD, with promising reports using stem cells for ILD patients. This Phase IIIa open-label trial involves intravenous transfusion of allogenic adipose tissue-derived mesenchymal stem cells AD-MSC in 10 patients with refractory or rapidly progressive ILD due to CTD. The first 3 participants will receive a low-dose infusion once if no adverse effects occur after 4 weeks, the next 4 to 7 participants will receive medium-dose infusions twice if still no adverse effects after 4 weeks, the last 2 to 3 participants will receive high-dose infusions three times. The goal is to improve outcomes and find the best dose of AD-MSC therapy. Participants will undergo initial evaluations before treatment, receive the stem cell infusions during admission, and then be followed up for safety and effectiveness for 48 weeks after the last infusion. Researchers will monitor safety throughout and assess lung function and other health indicators to evaluate treatment impact. The total study period includes treatment and nearly a year of post-infusion observation to track outcomes and any adverse effects.

Researchers are studying both adult- and childhood-onset myositis, an inflammatory muscle disease that can damage muscles and other organs, causing significant disability. The study aims to better understand the causes, immune system changes, and medical issues linked to myositis by evaluating children and adults with polymyositis, dermatomyositis, or related conditions. Healthy children and adults will also be included as control subjects for comparison. Participants will undergo a full medical history, physical exam, and review of medical records along with blood and urine tests. They may choose to participate in an additional evaluation lasting 1 to 5 days that can include muscle strength and joint movement tests, skin assessments, MRI scans of leg muscles, swallowing and speech studies, lung and heart function tests, endocrine and eye exams, nutrition assessments, muscle ultrasound, electromyography, and muscle or skin biopsies. Some patients may have a single evaluation, while others may return for follow-up visits up to one year. Throughout the study, participants will complete questionnaires and physical assessments to track their health and abilities. Healthy children will have similar tests including medical history, brief physical exams, swallowing and speech assessments, and muscle mass evaluation. The main outcome measure is a physicians global assessment at enrollment and during study visits. This observational study allows participants to contribute valuable information about myositis and related conditions over time.

Researchers are investigating the use of anti-CD19 CAR T-cell therapy as a new treatment approach for serious systemic autoimmune diseases that are difficult to treat, including Systemic Lupus Erythematosus SLE, Systemic Sclerosis SSc, DermatomyositisPolymyositis DMPM, and ANCA Associated Vasculitis AAV. These conditions involve harmful B cell activity and often do not respond well to current treatments, leading to severe health risks. This open-label, phase I basket study aims to assess the safety, feasibility, and early effectiveness of this therapy by monitoring adverse effects, infection rates, and disease response over 24 weeks in eight participants. Participants will receive a single intravenous infusion of an investigational product called CD19-CARLenti, which consists of their own T cells modified to target CD19-positive B cells. The T cells are collected through leukapheresis and processed using specialized equipment before infusion. The study includes pre-treatment procedures such as lymphodepletion, with all treatments and visits conducted at specialized hospital departments. The therapy targets a common disease mechanism across the four autoimmune conditions included in this basket trial. During the study, participants will have regular evaluations to monitor for side effects like cytokine release syndrome and neurotoxicity within the first 4 weeks, as well as infections and blood cell changes over the full 24-week period. Researchers will also measure how long the CAR T cells and B cell depletion persist in the blood and track changes in disease-related antibodies. The primary outcomes include safety events and overall disease response at 24 weeks. Participants will be closely followed through outpatient visits and laboratory tests throughout the study period.