The Efficacy and Safety of Telitacicept in the Treatment of Early Diffuse Cutaneous Systemic Sclerosis: a Multicenter, Open-label, Randomized Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 9
- 主要终点
- Percentage of Participants With Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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^
- •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).
研究组 & 干预措施
Mycophenolate Mofetil + Telitacicept
All patients who enroll in this trial will receive mycophenolate mofetil (MMF), which is a drug commonly given to patients with systemic sclerosis in clinical practice. Participants will be treated with MMF 0.5g twice a day for 48 weeks. Telitacicept will be subcutaneously injected at a dose of 160mg per week, lasting for 48 weeks.
干预措施: Telitacicept (Drug)
Mycophenolate Mofetil + Telitacicept
All patients who enroll in this trial will receive mycophenolate mofetil (MMF), which is a drug commonly given to patients with systemic sclerosis in clinical practice. Participants will be treated with MMF 0.5g twice a day for 48 weeks. Telitacicept will be subcutaneously injected at a dose of 160mg per week, lasting for 48 weeks.
干预措施: Mycophenolate Mofetil (Drug)
Mycophenolate Mofetil
Participants will be treated with MMF 0.5g twice a day for 48 weeks.
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Week 52
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 48
时间窗: Baseline, Week 48
Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.
次要结局
- Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24(Baseline, Week 24)
- Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted at Week 24 and Week 48(Week 24 and 48)
- Change From Baseline in Physician's Global Assessment at Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) at Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Tender Joint Counts at Week 24 and Week 48(Baseline, Week 24 and 48)
- Percentage of Participants Who Improved in Modified Rodnan Skin Score (mRSS) by ≥20%, ≥40%, ≥60% From Baseline to Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Swollen Joint Counts at Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Digital Ulcer Counts at Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percent Predicted (Corrected For Hemoglobin) at Week 24 and Week 48(Week 24 and 48)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24 and Week 48(Baseline, Week 24 and 48)
- American College of Rheumatology Composite Response Index for Systemic Sclerosis (ACR-CRISS) and Revised ACR-CRISS at Week 24 and 48(Week 24 and 48)
- Change From Baseline in Patient's Global Assessment at Week 24 and Week 48(Baseline, Week 24 and 48)
- Change From Baseline in Short Form-36 (SF-36) Questionnaire at Week 24 and Week 48(Baseline, Week 24 and 48)