Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus

A Phase I, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Telitacicept in Chinese Subjects With Systemic Lupus Erythematosus (SLE)

This is a multi-center, open-label, phase I study.

The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.

Inclusion Criteria:

1. Subjects who give consent to this study participation and sign informed consent form;
2. Males and females, between the ages of 18 and 65 years old, inclusive, at the screening visit;
3. Diagnosis of SLE as defined by the American College of Rheumatology (ACR) 1997 criteria, with 4 or more of the 11 ACR criteria present;
4. SELENA-SLEDAI score ≥8 points with a clinical SELENA-SLEDAI score ≥6 points if low complement levels and/or anti-ds-DNA antibodies are present at the screening visit;
5. Subjects with unequivocally positive test for anti-nuclear antibody (ANA) and/or anti-ds-DNA serum antibody;
6. Be on a SLE standard treatment regimen (and remain stable) for a period of at least 30 days prior to Day 0. The standard regimen consists of the following medication(s) (alone or in combination)：corticosteroids, anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), other immunosuppressive or immunomodulatory agents including azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, cyclosporine.

Exclusion Criteria:

1. Subjects with severe lupus kidney disease (defined by proteinuria >6g/24h or serum creatinine >2.5mg/dL or serum creatinine >221μmol/L) or active nephritis requiring prohibited medications, or subjects requiring hemodialysis or prednisone (or its equivalent)≥100mg/d for a period of ≥14 days within 8 weeks of Day 0;

2. Central nervous system (CNS) disease associated with lupus or not [including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), encephalitis, CNS angiitis] within 8 weeks prior to the screening visit;

3. Laboratory abnormalities including, but not limited to the following:

   1. ALT/AST≥2×upper limit of normal (ULN);
   2. endogenous creatinine clearance rate<30 mL/min;
   3. white blood cell count<2.5×10^9/L;
   4. hemoglobin<85 g/L;
   5. platelet count<50×10^9/L;

4. Active hepatitis or a history of severe liver disease at the screening visit. Positive test for Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibodies (HCVAb). If anti-HBcAb result is positive while HBsAg result is negative, hepatitis B virus (HBV)-(DNA) test will be performed. If HBV-DNA result is negative, the patient is eligible;

5. Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers;

6. Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study;

7. History of allergy to humanized biological products;

8. Subjects who received live vaccine within 28 days of Day 0;

9. Participation in any other investigational study drug trial in the past 28 days or 5 half-lives, whichever was longer, prior to Day 0. Subjects who participated in a clinical trial on B-cell-targeted drug, or tumor necrosis factor inhibitor, or interleukin receptor blocker within 12 months prior to Day 0 would be excluded;

10. Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0;

11. Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0;

12. Subjects who received intravenous immune globulin (IVIG), or high dose prednisone or its equivalents (≥100mg/d) for a period of ≥ 14 days, or plasma exchange within 28 days prior to Day 0;

13. Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0;

14. Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit;

15. Subjects with depression or suicidal thoughts;

16. Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..