a study of gnc-038 tetra-specific antibody injection in patients with systemic lupus erythematosus

Conditions: Systemic Lupus Erythematosus

Summary: this study is a randomized, controlled, phase i clinical study with safety, efficacy, and pharmacokinetic/pharmacodynamic characteristics in patients with systemic lupus erythematosus.

this study is divided into a phase ia study and a phase ib study. the phase ib study has a randomized controlled design with a placebo control group. the phase ia study has a single-arm design, and the phase ib study will be carried out on the basis of the phase ia study.

Eligibility criteria:
inclusion criteria: 1. subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. no gender limit; 3. age: ≥18 years old and ≤75 years old; 4. life expectancy greater than 6 months; 5. sle was diagnosed according to the 2019 eular/acr revised criteria; 6. patients with moderate to severe systemic lupus erythematosus, sledai-2k score \&gt at screening; 7 points; 7. a stable standard-of-care regimen was maintained for at least 30 days before the first dose; 8. ana ≥ 1:80 or anti-dsdna antibody higher than the upper limit of normal range (uln) as determined by central laboratory at screening; 9. the presence of cd19+ b cells in the peripheral blood of the patient; 10. the organ function level before the first administration met the requirements; 11. female subjects of childbearing potential or male subjects with a fertile partner must use highly effective contraception from 7 days before the first dose until 24 weeks after the termination of treatment and should commit not to donate eggs (eggs, oocytes)/sperm for assisted reproduction for 1 year after the last study treatment. female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose; 12. participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures. exclusion criteria: 1. severe lupus nephritis within 8 weeks before screening; 2. she had uncontrolled lupus crisis within 8 weeks before screening and was not suitable for the study as assessed by the investigator; 3. active encephalopathy or psychosis within 6 months before screening; 4. primary diagnosis of different autoimmune or inflammatory diseases; 5. b cell-depleting therapy within 6 months before initiation of gnc-038 treatment; 6. received car-t therapy within 6 months before gnc-038 treatment; 7. cytokine-targeting biologic agents used within 12 weeks before dose administration; 8. use of anti-tumor necrosis factor drugs within 8 weeks before administration; 9. use of any jak inhibitor within 2 weeks before dosing; 10. receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug; 11. major organ transplantation history or hematopoietic stem cell/bone marrow transplantation; 12. presence of: 1) active hepatitis b at screening; 2) hepatitis c or hiv infection; 3) syphilis infection; 13. a history of any cardiovascular disease described in the protocol within 6 months before screening; 14. poorly controlled hypertension (systolic blood pressure ≥160 mmhg or diastolic blood pressure ≥100 mmhg); 15. prolonged qt interval at rest (qtcf \> 450 msec in men or \> 470 msec in women); 16. a history of ≥ grade 2 bleeding within 30 days before screening or the need for long-term continuous anticoagulant therapy; 17. patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of gnc-038; 18. women who are pregnant or breastfeeding; 19. have a history or evidence of suicidal thoughts within 6 months before signing icf, which is considered by the researcher to be a significant risk of suicide; 20. diagnosed with malignant tumor within 5 years before signing icf; 21. other situations of poor compliance, unwillingness or inability to comply with the study protocol as judged by the investigator; 22. history of splenectomy; 23. investigators considered a history of alcohol or drug abuse in the 12 months before screening; 24. any active infection requiring systemic antibiotic treatment within 2 weeks before or during screening; 25. a history of severe and/or disseminated viral infection; 26. active m. tuberculosis infection may be present.