Clinical Research Directory

C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Systemic Sclerosis (SSc) Refractory to Standard Therapy

This Phase 1b, multicenter, open-label study will evaluate the safety and efficacy of a single infusion of autologous anti-CD20/BCMA chimeric antigen receptor T cells (C-CAR168) following lymphodepleting chemotherapy in participants with refractory Systemic Sclerosis (SSc) who are not responding to standard therapy. Approximately 6-12 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of C-CAR168. Participants will be followed for 24 months (2 years) to evaluate safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, biomarkers, and preliminary efficacy results. Long-term safety follow-up for gene therapy-related events will continue for up to 15 years following CAR T-cell infusion.

Infusion of Allogeneic Stromal Mesenchymal Stem Cells From Wharton´s Jelly in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement to Treatment

Progressive SSc is an entity with limited therapeutic alternatives and a survival rate of less than 45% within the first 3 to 5 years. The disease causes severe limitations in quality of life, ranging from functional impairment to depression. Up to 20% of patients become refractory to conventional treatment with disease-modifying anti-rheumatic drugs (DMARDs) and cyclophosphamide therapy. This condition favors progression to visceral involvement, including gastrointestinal, pulmonary, and pulmonary hypertension manifestations. The latter, considered a poor prognostic factor, increases mortality in this patient population and drastically affects quality of life. For this reason, different therapeutic options have been considered, including cell transplantation and stem cell use. Among the options studied to date are stromal mesenchymal cells derived from Wharton's jelly. These cells have been administered via intravenous infusion or direct application in various disease scenarios, ranging from vascular involvement to interstitial lung disease and pulmonary hypertension, with promising results in terms of clinical progression, quality of life improvement, and prognostic indices. This therapy has demonstrated a favorable safety profile at the time of administration and a low rate of adverse events, with self-limiting fever being the most frequent event. Based on the above and considering the possibility of offering patients without therapeutic alternatives for the disease, in addition to palliative options, an intravenous infusion of stromal mesenchymal stem cells derived from Wharton's jelly is proposed for three patients with progressive SSc refractory to conventional therapy, with pulmonary involvement due to pulmonary hypertension. Under this premise, the research question posed in this study is: What are the effects of the infusion of allogeneic mesenchymal stromal cells derived from Wharton's jelly in patients with systemic sclerosis refractory to conventional treatment with methotrexate or cyclophosphamide, in a population of three patients with severe pulmonary involvement due to pulmonary hypertension?

Home Based Clinical Management of Interstitial Lung Disease in Systemic Rheumatic Diseases

The RMD-mILDer trial is a home monitoring strategy trial aiming to improve management of interstitial lung disease related to rheumatic diseases applying eHealth technology. It is planned as a 2 arm 54 week multi-centre randomised controlled trial to assess outcome of home monitoring with bi-weekly serial forced vital capacity- and patient reported outcome-measurements compared to standard of care with fixed-interval hospital visits in adult patients with rheumatic disease associated interstitial lung diseases.