Phase I/II Study of QEL-005 Autologous CD19-Targeting CAR T-Regulatory Cell Therapy in Patients with Diffuse Cutaneous Systemic Sclerosis and Difficult-to-Treat Rheumatoid Arthritis

The primary objective is to evaluate the safety and tolerability of a single dose of QEL-005, an autologous CAR T-regulatory cell therapy targeting CD19. The secondary objectives include assessing early signs of clinical activity in patients with diffuse cutaneous systemic sclerosis and patients with difficult to treat rheumatoid arthritis.

This clinical trial involves a total of 8 patients. The study population includes both male and female participants within the specified age ranges. The cohort consists of individuals diagnosed with diffuse cutaneous systemic sclerosis or difficult to treat rheumatoid arthritis. Inclusion requirements for those with systemic sclerosis involve meeting 2013 ACR-EULAR criteria, being serologically positive for antinuclear antibodies, and demonstrating insufficient response to disease-modifying antirheumatic drugs. Additionally, these patients must exhibit a modified Rodnan Skin Score of at least 15, evidence of lung fibrosis, and active disease. For those with rheumatoid arthritis, diagnosis must align with 2010 ACR-EULAR and 2021 EULAR criteria, showing clinically active disease and joint inflammation. All participants are required to have an Eastern Cooperative Oncology Group performance status grade of less than 3, adequate haematological, liver, and renal function, and a stable steroid dose prior to screening.

This is a single-arm, open-label, multi-centre, phase I/II, first-in-human study designed to evaluate the safety and clinical activity of QEL-005, an autologous CAR T-regulatory cell therapy targeting CD19. The research is conducted in patients with diffuse cutaneous systemic sclerosis or difficult to treat rheumatoid arthritis. The study includes a dose escalation part and an expansion part. The primary objective is to determine the safety and tolerability of a single intravenous administration of the study product. Evaluation of safety includes the monitoring of dose-limiting toxicities, treatment-emergent serious adverse events, and adverse events of special interest, alongside assessment of electrocardiogram, vital signs, and laboratory parameters. Following the initial infusion, participants are required to enter a 15-year follow-up period.

The experimental treatment consists of QEL-005, an autologous CAR T-regulatory cell therapy targeting CD19. This substance is administered via intravenous administration in the form of an infusion.

The assessment of clinical activity for the autologous CAR T-regulatory cell therapy, QEL-005, is conducted within the framework of a phase I/II study. Efficacy and clinical activity are evaluated through the observation of clinical responses in patients diagnosed with diffuse cutaneous systemic sclerosis and difficult to treat rheumatoid arthritis.