A Phase I, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Telitacicept in Chinese Subjects With Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 19
- 主要终点
- Time to reach Cmax (tmax) of Telitacicept
研究概览
简要总结
This is a multi-center, open-label, phase I study.
详细描述
The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who give consent to this study participation and sign informed consent form;
- •Males and females, between the ages of 18 and 65 years old, inclusive, at the screening visit;
- •Diagnosis of SLE as defined by the American College of Rheumatology (ACR) 1997 criteria, with 4 or more of the 11 ACR criteria present;
- •SELENA-SLEDAI score ≥8 points with a clinical SELENA-SLEDAI score ≥6 points if low complement levels and/or anti-ds-DNA antibodies are present at the screening visit;
- •Subjects with unequivocally positive test for anti-nuclear antibody (ANA) and/or anti-ds-DNA serum antibody;
- •Be on a SLE standard treatment regimen (and remain stable) for a period of at least 30 days prior to Day
- •The standard regimen consists of the following medication(s) (alone or in combination)：corticosteroids, anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), other immunosuppressive or immunomodulatory agents including azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, cyclosporine.
排除标准
- •Subjects with severe lupus kidney disease (defined by proteinuria >6g/24h or serum creatinine >2.5mg/dL or serum creatinine >221μmol/L) or active nephritis requiring prohibited medications, or subjects requiring hemodialysis or prednisone (or its equivalent)≥100mg/d for a period of ≥14 days within 8 weeks of Day 0;
- •Central nervous system (CNS) disease associated with lupus or not [including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), encephalitis, CNS angiitis] within 8 weeks prior to the screening visit;
- •Laboratory abnormalities including, but not limited to the following:
- •ALT/AST≥2×upper limit of normal (ULN);
- •endogenous creatinine clearance rate<30 mL/min;
- •white blood cell count<2.5×10^9/L;
- •hemoglobin<85 g/L;
- •platelet count<50×10^9/L;
- •Active hepatitis or a history of severe liver disease at the screening visit. Positive test for Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibodies (HCVAb). If anti-HBcAb result is positive while HBsAg result is negative, hepatitis B virus (HBV)-(DNA) test will be performed. If HBV-DNA result is negative, the patient is eligible;
- •Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers;
- •Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study;
- •History of allergy to humanized biological products;
- •Subjects who received live vaccine within 28 days of Day 0;
- •Participation in any other investigational study drug trial in the past 28 days or 5 half-lives, whichever was longer, prior to Day
- •Subjects who participated in a clinical trial on B-cell-targeted drug, or tumor necrosis factor inhibitor, or interleukin receptor blocker within 12 months prior to Day 0 would be excluded;
- •Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0;
- •Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0;
- •Subjects who received intravenous immune globulin (IVIG), or high dose prednisone or its equivalents (≥100mg/d) for a period of ≥ 14 days, or plasma exchange within 28 days prior to Day 0;
- •Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0;
- •Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit;
- •Subjects with depression or suicidal thoughts;
- •Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..
研究组 & 干预措施
Telitacicept Arm 1
Telitacicept 80mg, once a week for 24 weeks plus standard therapy
干预措施: Telitacicept (Biological)
Telitacicept Arm 1
Telitacicept 80mg, once a week for 24 weeks plus standard therapy
干预措施: standard therapy (Drug)
Telitacicept Arm 2
Telitacicept 160mg, once a week for 24 weeks plus standard therapy
干预措施: Telitacicept (Biological)
Telitacicept Arm 2
Telitacicept 160mg, once a week for 24 weeks plus standard therapy
干预措施: standard therapy (Drug)
Telitacicept Arm 3
Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy
干预措施: Telitacicept (Biological)
Telitacicept Arm 3
Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy
干预措施: standard therapy (Drug)
Telitacicept Arm 4
Telitacicept 240mg, once a week for 24 weeks plus standard therapy
干预措施: Telitacicept (Biological)
Telitacicept Arm 4
Telitacicept 240mg, once a week for 24 weeks plus standard therapy
干预措施: standard therapy (Drug)
Telitacicept Arm 5
Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy
干预措施: Telitacicept (Biological)
Telitacicept Arm 5
Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy
干预措施: standard therapy (Drug)
结局指标
主要结局
Time to reach Cmax (tmax) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
tmax is defined as time to reach Cmax of Telitacicept
Observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval (Ctrough)
时间窗: up to 42 days following the last dose of Telitacicept
Ctrough is defined as observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval
Average concentration (Cav) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
Average concentration of Telitacicept
Area under the curve from time zero to last quantifiable concentration (AUC 0-t) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
AUC 0-t is defined as area under the curve from time zero to last quantifiable concentration of Telitacicept
Area under the curve from time zero to tau (AUC 0-tau) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
AUC 0-tau is defined as area under the curve from time zero to tau of Telitacicept
Terminal elimination rate constant (λz) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
λz is defined as terminal elimination rate constant
Terminal elimination half-life (t1/2z) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
t1/2z is defined as terminal elimination half-life of Telitacicept
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
Vz/F is defined as apparent volume of distribution during the terminal phase after extravascular administration of Telitacicept
Peak plasma concentration (Cmax) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
Cmax is defined as peak plasma concentration of Telitacicept
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Telitacicept
时间窗: up to 42 days following the last dose of Telitacicept
CL/F is defined as apparent total body clearance of drug from plasma after extravascular administration of Telitacicept
次要结局
- Percentage of participants achieving a SLE Responder Index (SRI)(Week 4, 8, 12, 16, 20, and 24)
- Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in patient global assessment (PGA)(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in IgG(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in IgA(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in IgM(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in C3(Week 4, 8, 12, 16, 20, and 24)
- Change From Baseline to W24 in C4(Week 4, 8, 12, 16, 20, and 24)
- Number of Participants Experiencing Adverse Events (AEs)(up to 28 days following the last dose of Telitacicept)