A Study of GNC-038 Tetra-specific Antibody Injection in Patients With Systemic Lupus Erythematosus

A Randomized Controlled Phase I Clinical Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of GNC-038 Tetra-specific Antibody Injection in Systemic Lupus Erythematosus

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 Phase Ia and Phase Ib studies. The Phase Ia study adopts a single-arm design, while the Phase Ib study will be conducted on the basis of the Phase Ia study and features an open-label, randomized, active-controlled design, with belimumab as the control agent.

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.