Systemic lupus erythematosus
Conditions
Interventions
SIM0278 300 µg Q2W placebo group:SIM0278 300 µg Q2W placebo
SIM0278 300 µg Q2W group:SIM0278 300 µg Q2W
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to initiation of any study-specified procedures, and willing and able to comply with all outpatient/inpatient visits and study-related procedures. 2. Male or female, aged >= 18 years and = 40.0 kg. 4. Diagnosis of SLE according to the 2019 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria. 5. Positive ANA test result at screening or documented positive historical result (ANA titer >= 1:80 based on indirect HEp-2 immunofluorescence assay or solid-phase ANA immunoassay with at least equivalent performance), and/or positive anti-dsDNA serum antibody result (>= 30 IU/mL based on enzyme-linked immunosorbent assay). 6. Confirmed diagnosis of Class III or IV active LN with or without Class V disease according to the 2003/2018 ISN/RPS classification, based on kidney biopsy results obtained within 6 months prior to the screening period or during screening. 7. Urine protein/creatinine ratio (UPCR) >= 1.0 mg/mg measured at screening. 8. eGFR >= 45 mL/min/1.73 m……². 9. Subject must be receiving or willing to initiate induction therapy for LN. Induction therapy, defined to include high-dose glucocorticoids and MMF, should be initiated within 60 days prior to baseline or on the day of baseline. 10. Received at least one dose of IV methylprednisolone pulse (0.25-0.5 g/day) or equivalent for up to 3 days, followed by oral prednisone 0.5 mg/kg/day (maximum 40 mg/day); and MMF at therapeutic dose 1.5-2 g/day orally for the current active LN flare, within 60 days prior to baseline, during screening, or on the day of baseline. 11. Female subjects of childbearing potential must have a negative pregnancy test. 12. Female and male subjects are willing to use protocol-required contraceptive measures from the screening visit until the end of the study, and do not plan to become pregnant or donate sperm/eggs during this period. Contraceptive requirements do not apply to the following infertile subjects: surgically sterile (surgery performed at least 1 month prior to dosing), or postmenopausal females (naturally postmenopausal for >= 12 months, >= 50 years of age; clinical diagnosis of menopause after exclusion of pregnancy and other diseases that may cause amenorrhea; for females < 50 years of age, menopause must be confirmed with follicle-stimulating hormone level).
Exclusion criteria
Exclusion criteria: 1. Previous or current renal disease (other than LN) that, in the investigator's opinion, may interfere with LN assessment and disease activity evaluation (e.g., diabetic nephropathy). Subject is unable or unwilling to provide written informed consent and/or comply with study procedures. 2. Severe renal impairment: a) presence of oliguria (defined as documented urine output = 50% of glomeruli; (2) Doubling of serum creatinine for 2 consecutive months prior to screening; (3) Investigator judgment that the subject has rapidly progressive glomerulonephritis. 4. Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) or glomerulosclerosis involving more than 50% of renal tissue, or poor expected response to immunosuppressive therapy in the investigator's opinion. 5. Previous failure to respond to MMF/MPS induction therapy as determined by the investigator. 6. Cumulative dose of IV methylprednisolone pulse therapy > 3000 mg within 12 weeks prior to baseline. 7. Subject is receiving systemic corticosteroids (> 5 mg/day prednisone or equivalent) for conditions other than SLE or LN, such as acute asthma, inflammatory bowel disease, etc. 8. Previous non-response to treatment with IL-2 or IL-2 analogs (including clinical studies). 9. Use of any B-cell depleting therapy (e.g., rituximab or other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) within 9 months prior to screening. 10. Use of belimumab (anti-BAFF mAb), telitacicept (recombinant TACI-Fc fusion protein), abatacept (CTLA4-Fc Ig), anti-tumor necrosis factor-a (TNF-a) mAb, immunoglobulin (i.v./s.c.), or plasmapheresis within 3 months prior to screening or 5 elimination half-lives of the drug, whichever is longer. 11. Use of any other immunosuppressive agents within 1 month prior to baseline or 5 elimination half-lives of the drug, whichever is longer: e.g., intravenous or oral cyclophosphamide, calcineurin inhibitors (cyclosporine, voclosporin, tacrolimus), JAK inhibitors or other kinase inhibitors; thalidomide and/or methotrexate; azathioprine, mizoribine — must be discontinued prior to initiation of MPA/MMF. Concomitant use of other DMARDs is not permitted. 12. Vaccination (including inactivated, live, or attenuated vaccines) prohibited from 3 months prior to baseline until the end of the study. 13. Use of any other investigational drug/therapy within 3 months prior to baseline or 5 elimination half-lives of the drug, whichever is longer. 14. Planned or anticipated use of any prohibited medications or procedures during study treatment. 15. Active chronic or acute infection requiring systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to baseline; or superficial skin infection that may interfere with study assessments within 1 week prior to baseline (subject may be rescreened after infection resolution). 16. Known or suspected history of immunosuppression-related infections within 6 months prior to baseline (even if resolved), including but not limited to invasive opportunistic infections such as aspergillosis, coccidioidomycosis, histoplasmosis, HIV, listeriosis, pneumocystosis, tuberculosis or nontuberculous mycobacterial disease; or abnormally frequent recurrent or persistent infections. 17.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of multiple subcutaneous (SC) administrations of SIM0278 for the treatment of active lupus nephritis (LN) on the background of standard therapy.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics, PK;Pharmacodynamics, PD;Anti-Drug Antibodies; | — |
Countries
China
Contacts
Public ContactLi Mengtao
Peking Union Medical College Hospital
Outcome results
None listed