Efficacy and Safety of Telitacicept in the Treatment of Systemic Sclerosis

Inclusion Criteria:

• Men or women aged 18-70 years old.

• Systemic sclerosis, as defined by ACR/EULAR (American College ofRheumatology/European League Against Rheumatism) 2013 criteria.

• dcSSc (diffuse cutaneous systemic sclerosis) according to the LeRoy criteria.

• Disease duration of ≤ 18 months (defined as time from the first non-Raynaud'sphenomenon manifestation).

• ≥ 10 mRSS units at the screening visit.

• Negative serum pregnancy test in a woman of childbearing potential at the screeningvisit.

• Ability to render informed consent in accordance with institutional guidelines.

Exclusion Criteria:

• Limited scleroderma.

• Disease duration of greater than 3 years.

• Rheumatic autoimmune disease other than SSc.

• Systemic sclerosis-like illness associated with environmental agents such as vinylchloride, or bleomycin.

• Any prior history of renal crisis.

• Intermediate- or high-risk pulmonary arterial hypertension.

• Pulmonary disease with FVC < 50% of predicted or DLCO (hemoglobin-corrected) < 40%of predicted at screening or requires oxygen therapy.

• Underwent major surgery within 8 weeks prior to randomization or planned majorsurgery during the trial period.

• Use of immunosuppressive therapies, including methotrexate, azathioprine,hydroxychloroquine, leflunomide, tacrolimus, sirolimus, and mycophenolate mofetilwithin 4 weeks prior to randomization, and cyclophosphamide within 3 months prior torandomization.

• Use of other anti-fibrotic agents, including colchicine, D-penicillamine,thalidomide, nintedanib, pirfenidone, tyrosine kinase inhibitors (imatinib,nilotinib, dasatinib) within 4 weeks prior to randomization.

• Use of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily,or intravenous and intramuscular corticosteroid injections within 4 weeks prior torandomization.

• Use of Intravenous Immunoglobulin (IVIG) within 12 weeks within 4 weeks prior torandomization.

• Prior use of belimumab, rituximab, or other B-Cell depleting therapies ever.

• Use of other biologics or small molecule targeted therapies, including anakinrawithin 1 week prior to randomization, ixekizumab within 2 weeks prior torandomization, and infliximab, certolizumab pegol, golimumab, adalimumab, abatacept,tocilizumab within 8 weeks prior to randomization, and janus kinase inhibitorswithin 2 weeks prior to randomization.

• Prior use of other cell depletion therapies.

• Concurrent serious medical condition which in the opinion of the investigator makesthe patient inappropriate for this study such as severe central nervous systemdisease，severe heart failure, arrhythmia, unstable atherosclerotic cardiovasculardisease, severe GI involvement, severe hypertension or severe diabetes.

• Abnormal results in hepatitis B or hepatitis C testing indicating active or chronicinfection.

• Active tuberculosis (TB) or latent TB infection.

• Seropositive for human immunodeficiency virus (HIV) or known history of HIVinfection.

• Known active bacterial, viral, fungal, mycobacterial, or other infection，includingmajor episode of infection requiring hospitalization or treatment with IVantibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior toscreening.

• Primary or secondary immunodeficiency.

• IgA deficiency (<10 mg/dL) or IgG deficiency (<400 mg/dL).

• Participation in another clinical research study involving the evaluation of anotherinvestigational drug within 3 months of entry into this study.

• Any of the following at the screening visit: Hemoglobin <8.0 g/dL; WBC <3 x 10^9/L;Neutrophil <1.5 x 10^9/L; platelets <75 x 10^9/L; serum ALT or AST > 1.5 x ULN; TBil > ULN; eGFR < 40mL/min/1.73m^2.

• Malignant disease within 5 years prior to screening, with the exception ofexcised/cured local basal or squamous cell carcinoma of the skin or carcinoma insitu of the uterine cervix;

• Immunization with a live/attenuated vaccine within 4 weeks prior to randomization.

• Pregnant or breast feeding women or women of childbearing potential not willing touse adequate contraception.

• History of allergic or anaphylactic reactions to human, humanized, or murinemonoclonal antibodies.

• Immunization with a live/attenuated vaccine within 4 weeks prior to randomization.

• Patients anticipated to be non-compliant with the protocol requirements or expectednot to complete the trial as planned (e.g., those with psychiatric disorders,history of alcohol abuse, drug abuse, or substance misuse).