A Study of SCTB35 in Patients with Systemic Lupus Erythematosus

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SCTB35 in Patients with Systemic Lupus Erythematosus

This study is a multicenter Phase Ib/II clinical trial aimed at evaluating the safety, tolerability and efficacy of SCTB35 in patients with systemic lupus erythematosus (SLE).

This study contains the dose-escalation and dose-expansion parts. The escalation cohorts will be enrolled to explore the maximum tolerated dose and recommended phase II dose (RP2D). A Safety Review Committee (SRC) will review the accumulated safety data and other available data, and make a recommendation to each dose level of SCTB35 in the escalation cohorts. The expansion cohorts will be initiated after the RP2D is confirmed, and to further compare the preliminary efficacy and safety of SCTB35 at appropriate dose levels recommended by SRC.

Inclusion Criteria:

1. Age 18-75 years；

2. Diagnosed with SLE for ≥12 weeks prior to screening (2019-ACR/EULAR criteria);

3. SLEDAI-2K ≥ 8 at screening, or ≥6 if there is hypocomplementemia or elevated anti-dsDNA antibody levels;

4. Positive for ANA (1:80) or positive for anti-dsDNA and/or anti-Sm antibodies within the last 12 months or at screening;

5. Currently receiving ≥1 stable dose of standard treatment: oral corticosteroids, antimalarials, or conventional immunosuppressive drugs

   1. Stable corticosteroid dose for ≥4 weeks prior to baseline;
   2. Stable dose of antimalarial drugs for ≥4 weeks prior to baseline;
   3. Stable dose of immunosuppressive agents for ≥4 weeks prior to baseline;

6. All male participants or females of reproductive potential must agree to use reliable contraception with their partner from signing the ICF through 6 months after the last dose of the study drug;

7. Understanding of the study procedures and voluntary signing of the informed consent form.

Exclusion Criteria:

1. Severe active or unstable lupus-related neuropsychiatric disorders;

2. Other autoimmune diseases that may interfere with efficacy evaluation;

3. Catastrophic antiphospholipid syndrome;

4. Received treatments that may affect the drug's effect:

5. Received live vaccines or attenuated vaccines within 28 days prior to baseline or screening;

6. Clinically significant bleeding risk;

7. Abnormal laboratory results:

   1. AST or ALT >2.5 x ULN;
   2. Total bilirubin >1.5 x ULN;
   3. ANC <1.5x10⁹/L;
   4. Platelets <75x10⁹/L;
   5. Hemoglobin <100g/L;

8. eGFR <30 mL/min/1.73 m²;

9. Positive serum HCG;

10. Received any investigational treatment within 30 days prior to baseline or within 5 half-lives of the investigational drug (whichever is longer);

11. Participants with recurrent, chronic, or other active infections as assessed by the investigator;

12. Severe or uncontrolled disease, which would prevent participation in the study;

13. Positive viral serology tests, including HIV, HCV, and HBV;

14. Tuberculosis screening: Known active tuberculosis or latent tuberculosis infection (LTBI);

15. Any type of active infection except nail bed fungal infections;

16. Severe infections;

17. History of progressive multifocal leukoencephalopathy (PML);

18. Diagnosed with type 1 or type 2 diabetes with poor control;

19. Uncontrolled hypertension (systolic >140 mmHg or diastolic >90 mmHg);

20. History of malignancy within 5 years prior to baseline;

21. Alcohol abuse or drug misuse within 12 months prior to screening;

22. Intolerance to the study drug or contraindications, including a history of severe allergic reactions to monoclonal antibodies or any component of SCTB35 injection;

23. Required hospitalization for major surgery within 4 weeks prior to screening or within 12 weeks post-study drug administration;

24. Participants with mental disorders or poor compliance;

25. Severe lupus nephritis;

26. History of solid organ or hematopoietic stem cell/bone marrow transplant, or expected to undergo transplant surgery during the study;

27. Pregnant or breastfeeding;

28. Any other condition that the investigator deems unsuitable for participation in the study.