A Phase II, multi-part, three-year, randomized, open-label, assessor-blinded, active-controlled, multicenter study to evaluate the efficacy and safety of rapcabtagene autoleucel versus rituximab treatment in participants with severe refractory diffuse cutaneous systemic sclerosis (CYTB323K12201) (CAR-T)

The purpose of this trial is to learn about the effect of YTB323 compared with rituximab in people with difficult to treat severe diffuse cutaneous systemic sclerosis (dcSSc) leading to organ failure and may lead to death. YTB323 is being tested for its effects on dcSSc. It is a type of treatment called chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, a person’s T cells are collected, modified in the lab to identify, and destroy immune B cells, and then put back into the person’s body. Before giving the YTB323 CAR T-cell therapy, people often receive conditioning treatment to reduce the count of the type of blood cells called lymphocytes and improve the chances of this YTB323 CAR T-cell therapy working. The conditioning treatment used in this trial includes two chemotherapy drugs, fludarabine and cyclophosphamide. This conditioning treatment will make room in the body for the participant’s modified YTB323 CAR T-cells. This trial has 2 parts. 6 participants are expected to join Part 1 and 80 participants are expected to join Part 2. The main questions this trial aims to answer are: • How many participants show a response at Week 52 after receiving a single dose of YTB323? A response is based on the assessment of end organ worsening and improvement in skin thickening, lung function, and quality of life. • What adverse events are reported during the trial?