A Randomized, Positvel Controlled, Multicenter Study of Effects of Telitacicept vs Cyclophosphamide on Lupus Realted Interstitial Lung Disease
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Correlation between change from baseline at week 52 in forced vital capacity (FVC) [percentage (%) predicted]
研究概览
简要总结
Recent data indicate that Telitacicept is beneficial for lupus nephritis. Our goal is to determine whether Telitacicept is an effective and safe treatment, compared to standard-of-care Cyclophosphamide, for subclinical and clinical ILD in patients with early lupus.
详细描述
Pulmonary abnormalities are present in up to 60% of patients with SLE, and up to 10% of the patients will develop clinical interstitial lung disease (ILD). Recent data indicate that Telitacicept is beneficial for lupus nephritis. Our goal is to determine whether Telitacicept is an effective and safe treatment, compared to standard-of-care Cyclophosphamide, for subclinical and clinical ILD in patients with early lupus. The study also explores disease mechanisms in lungs and serum immunological interaction, to identify potential biomarkers for diagnosis, prognosis, and response to treatment of lupus-ILD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus;
- •Male or non-pregnant female aged ≥ 18 years;
- •Diagnosis by high-resolution lung CT (HRCT) is clearly consistent with interstitial lung disease (ILD);
- •FEV1/FVC%≥60% and diffusion function DLCO (measured value/estimated value) ≥40%;
- •Patients voluntarily participate in this trial, have good compliance, and have the ability to understand and sign informed consent before the study.
排除标准
- •Alanine aminotransferase and/or aspartate aminotransferase (ALT/AST) > 5 times the upper limit of normal;
- •severe chronic kidney disease (stage IV) or need for dialysis (estimated glomerular filtration rate (eGFR) < 30ml/min/1.73m2);
- •Hemoglobin < 80 g/L;
- •WBC < 2.0×10^9;
- •Platelet < 50×10^9;
- •Is pregnant or breastfeeding;
- •Expected transfer to another hospital in a non-study site within 4 weeks (possibility of loss to follow-up);
- •Life expectancy does not exceed 24 weeks;
- •Have a history of severe allergies;
- •Patients with other serious lung diseases or other clinically significant serious abnormalities in the lungs;
- •Are using antitumor drugs, other immunosuppressants or immunomodulatory therapies;
- •Significant pulmonary hypertension;
- •Previous clinical or echocardiographic evidence of significant right heart failure;
- •Right heart catheterization showing cardiac index ≤ 2 L/min/m2;
- •Pulmonary hypertension requiring treatment with epoprostenol/traprostacyclin.
- •Patients with severe cardiovascular disease:
- •myocardial infarction within 6 months;
- •Unstable angina within 6 months.
- •Risk of bleeding, any of the criteria listed below:
- •known genetic predisposition to bleeding;
- •Patients who require the following treatments:
- •i. Fibrinolytic therapy, full-dose therapeutic anticoagulation (e.g., vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin); ii. High-dose antiplatelet therapy. [Note: Prophylactic low-dose heparin or heparin flush solution (e.g., enoxaparin, 4000 I.U. S.C. per day) required for maintenance of indwelling intravenous access devices is not prohibited.) and prophylactic antiplatelet therapy (e.g., acetylsalicylic acid up to 325 mg/day, or clopidogrel at a dose of 75 mg/day, or other antiplatelet therapy at the same dose).
- •History of hemorrhagic central nervous system (CNS) events within 12 months;
- •Any of the following conditions within a period of 3 months:
- •hemoptysis or hematuria;
- •Active gastrointestinal bleeding or gastrointestinal ulcers;
- •Have previously undergone hematopoietic stem cell transplantation (HSCT), or plan to receive HSCT in the following year, or plan to undergo major surgery.
- •Women who are pregnant, breastfeeding or planning to become pregnant during the test;
- •28 days before administration or 3 months after administration, women of childbearing age are unwilling or unable to use highly effective contraceptive methods;
- •According to the investigator's point of view, the patient has alcohol or drug abuse;
- •History of dysphagia or any gastrointestinal disease that affects drug
- •Patients with contraindications to the use of tatacept;
- •Subjects deemed unsuitable for participation in the study by the investigator.
研究组 & 干预措施
glucocorticoids and/or immunosuppressants other than CYC+ treatment with the Telitacicept group
Telitacicept 160mg sc qw, plus standard of care therapy including glucocorticoids and/or immunosuppressants other than CYC sush as , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the cyclophosphamide usage was included in the group.
干预措施: Methylprednisolone (Corticosteroid) (Drug)
glucocorticoids and/or immunosuppressants other than CYC+ treatment with the Telitacicept group
Telitacicept 160mg sc qw, plus standard of care therapy including glucocorticoids and/or immunosuppressants other than CYC sush as , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the cyclophosphamide usage was included in the group.
干预措施: Immunosuppressant other than CYC (Drug)
glucocorticoids and/or immunosuppressants other than CYC+ treatment with the Telitacicept group
Telitacicept 160mg sc qw, plus standard of care therapy including glucocorticoids and/or immunosuppressants other than CYC sush as , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the cyclophosphamide usage was included in the group.
干预措施: Telitacicept Freeze-dried powder Injection 80mg (Drug)
glucocorticoids plus CYC and/or other immunosuppressants
All patient in this group were administered with cyclophosphamide. The other immunosuppressants in this group include , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the biological agents like belimumab (Benlysta), anifrolumab (Saphnelo), telitacicept (TaiAi), tocilizumab (Actemra) and rituximab (Rituxan) was included in this group.
干预措施: Methylprednisolone (Corticosteroid) (Drug)
glucocorticoids plus CYC and/or other immunosuppressants
All patient in this group were administered with cyclophosphamide. The other immunosuppressants in this group include , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the biological agents like belimumab (Benlysta), anifrolumab (Saphnelo), telitacicept (TaiAi), tocilizumab (Actemra) and rituximab (Rituxan) was included in this group.
干预措施: Immunosuppressant other than CYC (Drug)
glucocorticoids plus CYC and/or other immunosuppressants
All patient in this group were administered with cyclophosphamide. The other immunosuppressants in this group include , tacrolimus, Sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine. None of the biological agents like belimumab (Benlysta), anifrolumab (Saphnelo), telitacicept (TaiAi), tocilizumab (Actemra) and rituximab (Rituxan) was included in this group.
干预措施: Cyclophosphamide (CYC) (Drug)
结局指标
主要结局
Correlation between change from baseline at week 52 in forced vital capacity (FVC) [percentage (%) predicted]
时间窗: At baseline and at week 24, 52
Pulmonary function measurement (FEV1/FVC% % post-treatment difference during baseline)
次要结局
- Correlation between change from baseline at week 52 in diffusing capacity for carbon monoxide (DLco) [percentage (%) predicted](At baseline and at week 24, 52)
- Anti-double-stranded DNA antibody conversion ratio(At baseline and at week 12, 24, and 52)
- Complement C3 and C4 levels return to normal ratios(At baseline and at week 12, 24, and 52)
- Six minutes walking distance(At baseline and at week 12, 24, and 52)
- Changes from baseline in cumulative corticosteroid dose at week 52(At baseline and at week 52)
- Krebs von den Lungen-6(At baseline and at week 12, 24, and 52)
研究者
YIKAI YU
the Deputy Chief Physician
Tongji Hospital