Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Biological: TelitaciceptDrug: standard therapy
- Registration Number
- NCT05247203
- Lead Sponsor
- RemeGen Co., Ltd.
- Brief Summary
This is a multi-center, open-label, phase I study.
- Detailed Description
The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 92
- 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 0. 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.
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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;
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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;
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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;
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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;
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Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers;
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Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study;
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History of allergy to humanized biological products;
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Subjects who received live vaccine within 28 days of Day 0;
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Participation in any other investigational study drug trial in the past 28 days or 5 half-lives, whichever was longer, prior to Day 0. 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;
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Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0;
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Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0;
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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;
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Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0;
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Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit;
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Subjects with depression or suicidal thoughts;
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Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telitacicept Arm 1 Telitacicept Telitacicept 80mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 1 standard therapy Telitacicept 80mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 2 Telitacicept Telitacicept 160mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 2 standard therapy Telitacicept 160mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 3 Telitacicept Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy Telitacicept Arm 3 standard therapy Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy Telitacicept Arm 4 Telitacicept Telitacicept 240mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 4 standard therapy Telitacicept 240mg, once a week for 24 weeks plus standard therapy Telitacicept Arm 5 Telitacicept Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy Telitacicept Arm 5 standard therapy Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy
- Primary Outcome Measures
Name Time Method Time to reach Cmax (tmax) of Telitacicept 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) 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 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 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 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 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 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 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 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 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
- Secondary Outcome Measures
Name Time Method Percentage of participants achieving a SLE Responder Index (SRI) Week 4, 8, 12, 16, 20, and 24 Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA-SLEDAI score, and no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.
Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points Week 4, 8, 12, 16, 20, and 24 SELENA-SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105.
Change From Baseline to W24 in IgA Week 4, 8, 12, 16, 20, and 24 Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in patient global assessment (PGA) Week 4, 8, 12, 16, 20, and 24 PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).
Change From Baseline to W24 in IgG Week 4, 8, 12, 16, 20, and 24 Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in IgM Week 4, 8, 12, 16, 20, and 24 Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in C3 Week 4, 8, 12, 16, 20, and 24 Complement (C3/C4) are proteins that are part of the immune system.
Change From Baseline to W24 in C4 Week 4, 8, 12, 16, 20, and 24 Complement (C3/C4) are proteins that are part of the immune system.
Number of Participants Experiencing Adverse Events (AEs) up to 28 days following the last dose of Telitacicept Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Trial Locations
- Locations (19)
Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
The Second Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
The People's Hospital of Xinjiang Uygur Autonomous Region
🇨🇳Ürümqi, Xinjiang, China
The First Affiliated Hospital of University of Science and Technology of China
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
General Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi, China
The Second Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
The Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
Shanxi Bethune Hospital
🇨🇳Taiyuan, Shanxi, China
The First People's Hospital of Yunnan Province
🇨🇳Kunming, Yunnan, China