Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a multi-center, open-label, phase I study.

Detailed Description
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The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.

Official Title
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A Phase I, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Telitacicept in Chinese Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Telitacicept
* Drug: standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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: 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 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..

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept Arm 1<br>Telitacicept 80mg, once a week for 24 weeks plus standard therapy | Biological: Telitacicept<br>* subcutaneous injection<br>* Other names: RC18;Drug: standard therapy<br>* 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.<br>|
| Experimental: Telitacicept Arm 2<br>Telitacicept 160mg, once a week for 24 weeks plus standard therapy | Biological: Telitacicept<br>* subcutaneous injection<br>* Other names: RC18;Drug: standard therapy<br>* 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.<br>|
| Experimental: Telitacicept Arm 3<br>Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy | Biological: Telitacicept<br>* subcutaneous injection<br>* Other names: RC18;Drug: standard therapy<br>* 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.<br>|
| Experimental: Telitacicept Arm 4<br>Telitacicept 240mg, once a week for 24 weeks plus standard therapy | Biological: Telitacicept<br>* subcutaneous injection<br>* Other names: RC18;Drug: standard therapy<br>* 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.<br>|
| Experimental: Telitacicept Arm 5<br>Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy | Biological: Telitacicept<br>* subcutaneous injection<br>* Other names: RC18;Drug: standard therapy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Telitacicept, Pharmacokinetics, Lupus Erythematosus, Systemic, Connective Tissue Diseases, Autoimmune Diseases