Systemic Lupus Erythematosus
Conditions
Keywords
Systemic Lupus Erythematosus, Telitacicept, Pharmacokinetics, Lupus Erythematosus, Systemic, Connective Tissue Diseases, Autoimmune Diseases
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.
Interventions
BIOLOGICALTelitacicept
subcutaneous injection
DRUGstandard therapy
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.
Sponsors
RemeGen Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who give consent to this study participation and sign informed consent form; 2. Males and females, between the ages of 18 and 65 years old, inclusive, at the screening visit; 3. Diagnosis of SLE as defined by the American College of Rheumatology (ACR) 1997 criteria, with 4 or more of the 11 ACR criteria present; 4. 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; 5. Subjects with unequivocally positive test for anti-nuclear antibody (ANA) and/or anti-ds-DNA serum antibody; 6. 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
1. 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; 2. 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; 3. Laboratory abnormalities including, but not limited to the following: 1. ALT/AST≥2×upper limit of normal (ULN); 2. endogenous creatinine clearance rate\<30 mL/min; 3. white blood cell count\<2.5×10\^9/L; 4. hemoglobin\<85 g/L; 5. platelet count\<50×10\^9/L; 4. 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; 5. Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers; 6. Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study; 7. History of allergy to humanized biological products; 8. Subjects who received live vaccine within 28 days of Day 0; 9. 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; 10. Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0; 11. Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0; 12. 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; 13. Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0; 14. Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit; 15. Subjects with depression or suicidal thoughts; 16. Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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. |
| 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. |
Countries
China
Outcome results
None listed