Clinical Research Directory

Combining Gene Editing and iPS to Study and Treat Monogenic Autoinflammatory Diseases

Type I interferonopathies (T1I) are rare autoinflammatory diseases characterized by dysregulated type I interferon signaling, leading to severe multisystem inflammation, including skin and lung involvement. STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant T1I associated with severe systemic inflammation, skin ulcers, and progressive interstitial lung disease. Current treatments are often insufficient, highlighting the need for novel therapeutic strategies. This project aims to develop patient-derived induced pluripotent stem cell (iPSC) models, combined with somatic cell differentiation and 3D organoid technologies, to investigate SAVI pathogenesis and assess the feasibility and efficacy of gene editing (GE). By enabling precise correction of disease-causing mutations, GE may overcome the limitations of conventional gene replacement approaches and provide a proof of concept for future targeted therapies.

A Study to Test How Well BI 3000202 is Tolerated by People With Type 1 Interferonopathies

This study is open to adults with selected type 1 interferonopathies. People can join the study if they have Aicardi-Goutières syndrome (AGS), Coatomer subunit alpha (COPA) syndrome, Familial chilblain lupus (FCL), or another type 1 interferonopathy with a specific gene mutation. The purpose of this study is to find out how BI 3000202 is tolerated in people with selected type 1 interferonopathies. Participants take a lower dose of BI 3000202 as tablets for 4 weeks. Afterwards, they take a higher dose of BI 3000202 as tablets for 36 weeks. They may continue with the study treatment until every participant has completed 40 weeks of treatment (about 9 months). The participants may also continue their regular treatment for their condition during the study. During this study, participants visit the study site 13 times or more, depending on when they start their participation. The doctors check the health of the participants and note any health problems that could have been caused by BI 3000202.

Investigation of Type I Interferon Excess in Patients With Systemic Autoimmune Diseases and Genetic Type I Interferonopathies

Systemic autoimmune diseases associated with type I interferon (IFN-I) dysregulation, such as systemic lupus erythematosus, systemic sclerosis, myositis, and mixed or undifferentiated connective tissue diseases, and genetic type 1 interferonopathies are characterized by chronic and excession IFN-I signaling and production contributing to disease pathogenesis. Aberrant IFN-I production can be triggered through the activation of multiple signaling pathways, particularly those involving intracellular and extracellular RNA and DNA sensing receptors. We hypothesize that excessive IFN-I production results from an increased tonic activation state of nucleic acid sensors and/or an enhanced responsiveness of these sensors to endogenous nucleic acids, thereby sustaining pathological IFN-I signaling and chronic inflammation. The aim of this study is to characterize the type I interferon (IFN-I) response, defined by both the IFN-I gene signature and plasma IFN-α levels, following stimulation with a panel of ligands specific for DNA- and RNA-sensing pathways.

Phase 1b Safety Study of IMSB301 in Type 1 Interferonopathies

Open-Label Study (Phase Ib) of Type 1 Interferonopathy patients receiving IMSB301 monotherapy.