Efficacy and Safety of Telitacicept in the Treatment of Systemic Sclerosis

The Efficacy and Safety of Telitacicept in the Treatment of Early Diffuse Cutaneous Systemic Sclerosis: a Multicenter, Open-label, Randomized Controlled Study

This study is a prospective, open-label, randomized, controlled, multi-center clinical trial. The aim of this study is to investigate the efficacy and safety of Telitacicept in adults with early diffuse cutaneous systemic sclerosis (dcSSc), with Mycophenolate Mofetil (MMF) administered as a background treatment.

Inclusion Criteria:

• Men or women aged 18-70 years old.
• Systemic sclerosis, as defined by ACR/EULAR (American College of Rheumatology/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's phenomenon manifestation).
• ≥ 10 mRSS units at the screening visit.
• Negative serum pregnancy test in a woman of childbearing potential at the screening visit.
• 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 vinyl chloride, 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 major surgery during the trial period.
• Use of immunosuppressive therapies, including methotrexate, azathioprine, hydroxychloroquine, leflunomide, tacrolimus, sirolimus, and mycophenolate mofetil within 4 weeks prior to randomization, and cyclophosphamide within 3 months prior to randomization.
• 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 to randomization.
• Use of Intravenous Immunoglobulin (IVIG) within 12 weeks within 4 weeks prior to randomization.
• Prior use of belimumab, rituximab, or other B-Cell depleting therapies ever.
• Use of other biologics or small molecule targeted therapies, including anakinra within 1 week prior to randomization, ixekizumab within 2 weeks prior to randomization, and infliximab, certolizumab pegol, golimumab, adalimumab, abatacept, tocilizumab within 8 weeks prior to randomization, and janus kinase inhibitors within 2 weeks prior to randomization.
• Prior use of other cell depletion therapies.
• Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as severe central nervous system disease，severe heart failure, arrhythmia, unstable atherosclerotic cardiovascular disease, severe GI involvement, severe hypertension or severe diabetes.
• Abnormal results in hepatitis B or hepatitis C testing indicating active or chronic infection.
• Active tuberculosis (TB) or latent TB infection.
• Seropositive for human immunodeficiency virus (HIV) or known history of HIV infection.
• Known active bacterial, viral, fungal, mycobacterial, or other infection，including major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.
• 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 another investigational 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 of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ 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 to use adequate contraception.
• History of allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
• Immunization with a live/attenuated vaccine within 4 weeks prior to randomization.
• Patients anticipated to be non-compliant with the protocol requirements or expected not to complete the trial as planned (e.g., those with psychiatric disorders, history of alcohol abuse, drug abuse, or substance misuse).