Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

Prior treatment

• within 5 half-life cycles of the last administration of an investigational product

Other illness

• history of autologous stem cell transplantation
• with other autoimmune comorbidities that need systemic treatment
• with a history of severe drug allergy
• with malignant tumors, except for nonmelanoma skin cancer, in situ cervical cancer, bladder cancer, breast cancer which has been disease free for more than 2 years
• with psychiatric diseases or severe cognition dysfunctions
• a history of CAR-T therapy or other gene-modified T cell targeted therapies
• other conditions that are not suitable for enrollment of the study in the judgement of the investigator
• the use of any live vaccines against infections within one month of the screening
• with any manifestations of active tuberculosis at screening

Other

• NYHA class IV
• FVC predicted \< 45% or DLCO predicted \< 40%
• abnormalities on HRCT not attributable to systemic sclerosis
• with manifestations of renal crisis
• with congenital immunoglobulin deficiency
• pregnant, lactation or plan to be pregnant within one year

• voluntary to sign the ICF
• aged between 18-65 years old (inclusive)
• diagnosed with diffuse systemic sclerosis according to 2013 ACR Systemic Sclerosis Classification Criterion
• meet the definitions of refractory/progressive as below:
  • refractory: non-respondent to or disease recurrence after remission with conventional therapies. Conventional therapies are defined as treated for more than 6 months with low dose steroids (≤ 15 mg prednisone equivalent), cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporin or biologics such as rituximab, belimumab, telitacicept, tocilizumab;
  • progressive: having below manifestations within 6 months
  • mRSS increases by \>= 3
  • FVC decreases by \> 10% or FVC decreases by \> 5% and DLCO decreases by \> 15%
• without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis
• available vascular access for leukapheresis
• major organ functions:
  • Renal function: CrCl ≥50 ml/min (Cockcroft/Gault equation)
  • Bone marrow function: ANC ≥ 1000/uL, absolute lymphocyte count ≥100/uL, Hb ≥90 g/L, Platelet count ≥75 x 10\^9/L. Blood transfusion and infusion of growth factors within 7 days of eligibility assessment are not allowed.
  • Liver function: ALT ≤ 3 x ULN, AST ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (in case of Gilbert syndrome, total bilirubin ≤ 3 x ULN)
  • Coagulation: INR ≤ 1.5 x ULN, PT ≤1.5 x ULN
  • Cardiac function: LVEF ≥ 55%
• negative result of serum β-hCG measurement for women of childbearing potential at screening and within 48 hours of the first dose of lymphodepletion
• Female subjects with childbearing potential or male subjects with partners of childbearing potential should adopt medically effective contraception or abstinence from enrollment to 2 years after the end of the study; female subjects with childbearing potential should have a negative serum hCG test within 7 days of enrollment and not in lactation