Systemic Lupus Erythematosus
Conditions
Keywords
systemic lupus erythematosus, pediatrics, PK
Brief summary
This is a multi-center, open-label, phase 1 study.
Detailed description
The purpose of this study is to evaluate the pharmacokinetics (PK) of multiple doses of Telitacicept in subjects with childhood-onset systemic lupus erythematosus (cSLE) on a background of standard of care therapy and explore the safety and efficacy of Telitacicept in patients with cSLE.
Interventions
BIOLOGICALTelitacicept
12-17 years old: Telitacicept 2.5 mg/kg (with a maximum dose of 160 mg) subcutaneously once a week plus SOC for 12 weeks. 5-11years old: Telitacicept 3.0-3.5 mg/kg (with a maximum dose of 160 mg) subcutaneously once a week plus SOC for 12 weeks.
Sponsors
RemeGen Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Fulfills SLICC 2012 or 2019 EULAR/ACR classification criteria for SLE. 2. 5-17 years of age when signing the informed consent. 3. Suject and/or legal guardian or parent provided written informed consent. 4. SELENA SLEDAI score ≥ 8 at screening. 5. Serum autoantibodies (ANA and/or anti ds-DNA) tested positive at screening. 6. Have been on a stable standard of care for SLE for at least 30 days prior to randomization. 7. Female patients are required to be non-pregnant, non-lactating or sterile. Main
Exclusion criteria
1. Have received Telitacicept at any time. 2. Have received any of the following therapies within 6 months of baseline: B-cell targeted treatment, e.g., belimumab, rituximab, abatacept, other investigational biologicals. 3. Have received any of the following therapies within 90 days of baseline: anti-TNF or anti-IL-6 therapy, interleukin-1 receptor antagonist, intravenous immunoglobulin (IVIG), plasmapheresis. 4. Have received any of the following therapies within 30 days of baseline: Intravenous cyclophosphamide, non-biological investigational agents (within 30 days of baseline or 5 half-lives, whichever is longer), newly added immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, high-dose prednisone or equivalent (\> 1.5 mg/kg/day) or any intramuscular or intravenous steroid. 5. Have received live vaccine within 30 days of baseline. 6. Participated in an interventional clinical trial within 6 months of screening. 7. Active CNS lupus requiring treatment within 60 days of baseline, including seizure, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis or CNS vasculitis. 8. Currently on kidney replacement therapy (hemodialysis, peritoneal dialysis) or in need of such therapy within 90 days of baseline. 9. eGFR\<30 mL/min/1.73m2. 10. Acute severe nephritis. 11. History of vital organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. 12. Significant unstable or uncontrolled acute or chronic diseases (cardiovascular, lung, hematology, gastrointestinal, liver, renal, neurologic, malignancy or infectious disease) that could be explained by causes other than SLE. 13 Have planned surgery, laboratory abnormalities, other diseases or conditions that, in the opinion of the investigator, makes the subject unsuitable for the study. 14\. History of malignant neoplasm in the past 5 years. 15. Primary immune deficiency. 16. Acute or chronic infections requiring treatment. 17. HIV or HCV positive. 18. Tuberculosis. 19.HBsAg/HbcAb positive. 20.HBcAb positive. 21.History of COVID-19 within 4 weeks prior to screening. 22.History of hospitalization due to severe Covid-19 within 12 months prior to screening. 23.History of allergy to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. 24.History of drug or alcohol abuse or dependence within 364 days prior to baseline. 25.Investigators believe that there are other factors that are not suitable for participating in the experiment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Telitacicept | up to 42 days following the last dose of Telitacicept | Cmax is defined as peak plasma concentration of Telitacicept |
| tmax of Telitacicept | up to 42 days following the last dose of Telitacicept | tmax is defined as time to reach Cmax of Telitacicept |
| Ctrough of Telitacicept | 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 |
| Cav of Telitacicept | up to 42 days following the last dose of Telitacicept | Average concentration of Telitacicept |
| AUC0-t of Telitacicept | up to 42 days following the last dose of Telitacicept | AUC0-t is defined as area under the curve from time zero to last quantifiable concentration of Telitacicept |
| 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 |
| λz of Telitacicept | up to 42 days following the last dose of Telitacicept | λz is defined as terminal elimination rate constant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SLE Responder Index 4 (SRI 4) | Week 4, Week 8, Week 12 | SRI 4 is defined as a. SELENA-SLEDAI score reduced from baseline by at least 4 points; b. no new BILAG A or no more than 1 BILAG B compared to baseline; c. physician's global assessment (PGA) increased from baseline by less than 0.3 points. |
| Proportion of subjects with SELENA-SLEDAI score reduced from baseline by at least 4 points. | Week 4, Week 8, Week 12 | The SELENA-SLEDAI is a tool for measuring the activity of systemic lupus. The total score ranges from 0-105, with a higher score representing a more significant degree of disease activity. |
| Change from baseline in PGA. | Week 4, Week 8, Week 12 | The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. |
| Change From Baseline in IgG | Week 4, Week 8, Week 12 | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. |
| Change From Baseline in IgA | Week 4, Week 8, Week 12 | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. |
| Change From Baseline in IgM | Week 4, Week 8, Week 12 | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. |
| Change From Baseline in C3 | Week 4, Week 8, Week 12 | Complement (C3/C4) are proteins that are part of the immune system. |
| Change From Baseline in C4 | Week 4, Week 8, Week 12 | Complement (C3/C4) are proteins that are part of the immune system. |
| Incidence of AEs | up to Week 12 | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORHongmei Song, M.D.
Peking Union Medical College Hospital
Outcome results
None listed