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This is a multi-center, open-label, phase I study.
The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Telitacicept Arm 1 | Experimental | Telitacicept 80mg, once a week for 24 weeks plus standard therapy |
|
| Telitacicept Arm 2 | Experimental | Telitacicept 160mg, once a week for 24 weeks plus standard therapy |
|
| Telitacicept Arm 3 | Experimental | Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy |
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| Telitacicept Arm 4 | Experimental | Telitacicept 240mg, once a week for 24 weeks plus standard therapy |
|
| Telitacicept Arm 5 | Experimental | Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Telitacicept | Biological | subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma concentration (Cmax) of Telitacicept | Cmax is defined as peak plasma concentration of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Time to reach Cmax (tmax) of Telitacicept | tmax is defined as time to reach Cmax of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval (Ctrough) | Ctrough is defined as observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval | up to 42 days following the last dose of Telitacicept |
| Average concentration (Cav) of Telitacicept | Average concentration of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Area under the curve from time zero to last quantifiable concentration (AUC 0-t) of Telitacicept | AUC 0-t is defined as area under the curve from time zero to last quantifiable concentration of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Area under the curve from time zero to tau (AUC 0-tau) of Telitacicept | AUC 0-tau is defined as area under the curve from time zero to tau of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Terminal elimination rate constant (λz) of Telitacicept |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of participants achieving a SLE Responder Index (SRI) | 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. | Week 4, 8, 12, 16, 20, and 24 |
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Inclusion Criteria:
Exclusion Criteria:
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:
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 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;
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..
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Bengbu Medical College | Bengbu | Anhui | 233004 | China | ||
| The First Affiliated Hospital of University of Science and Technology of China |
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| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D003240 | Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000722462 | telitacicept |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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|
| standard therapy | Drug | A 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. |
|
λz is defined as terminal elimination rate constant |
| up to 42 days following the last dose of Telitacicept |
| Terminal elimination half-life (t1/2z) of Telitacicept | t1/2z is defined as terminal elimination half-life of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Telitacicept | Vz/F is defined as apparent volume of distribution during the terminal phase after extravascular administration of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Telitacicept | CL/F is defined as apparent total body clearance of drug from plasma after extravascular administration of Telitacicept | up to 42 days following the last dose of Telitacicept |
| Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points | SELENA-SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105. | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in patient global assessment (PGA) | PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in IgG | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in IgA | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in IgM | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in C3 | Complement (C3/C4) are proteins that are part of the immune system. | Week 4, 8, 12, 16, 20, and 24 |
| Change From Baseline to W24 in C4 | Complement (C3/C4) are proteins that are part of the immune system. | Week 4, 8, 12, 16, 20, and 24 |
| Number of Participants Experiencing Adverse Events (AEs) | Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. | up to 28 days following the last dose of Telitacicept |
| Hefei |
| Anhui |
| 230001 |
| China |
| Peking Union Medical College Hospital | Beijing | Beijing Municipality | 100032 | China |
| The Second Affiliated Hospital of Guangzhou Medical University | Guangzhou | Guangdong | 510260 | China |
| Affiliated Hospital of Guilin Medical University | Guilin | Guangxi | 541001 | China |
| Affiliated Hospital of Hebei University | Baoding | Hebei | 071000 | China |
| The Second Hospital of Hebei Medical University | Shijiazhuang | Hebei | 050000 | China |
| Xiangya Hospital, Central South University | Changsha | Hunan | 410008 | China |
| The Second Xiangya Hospital of Central South University | Changsha | Hunan | 410011 | China |
| The First Hospital of China Medical University | Shenyang | Liaoning | 110001 | China |
| The First Affiliated Hospital of Xi'an Jiaotong University | Xi'an | Shaanxi | 710061 | China |
| Qilu Hospital of Shandong University | Jinan | Shandong | 250012 | China |
| Yantai Yuhuangding Hospital | Yantai | Shandong | 264200 | China |
| The Second Hospital of Shanxi Medical University | Taiyuan | Shanxi | 030001 | China |
| Shanxi Bethune Hospital | Taiyuan | Shanxi | 030032 | China |
| General Hospital of Tianjin Medical University | Tianjin | Tianjin Municipality | 300052 | China |
| The People's Hospital of Xinjiang Uygur Autonomous Region | Ürümqi | Xinjiang | 830001 | China |
| The First People's Hospital of Yunnan Province | Kunming | Yunnan | 650011 | China |
| The Second Affiliated Hospital of Zhejiang University | Hangzhou | Zhejiang | 310009 | China |