A Study of Telitacicept in Lupus Nephritis

A Phase Ⅱ, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Telitacicept in Lupus Nephritis

The purpose of this study is to evaluate the safety and efficacy of Telitacicept in adult patients with active lupus nephritis.

This is a phase 2, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of telitacicept versus placebo while taking standard of care (SOC) treatment in adult subjects with active proliferative lupus nephritis (LN).

Main Inclusion Criteria:

1. Males or females aged 18-75 years of age, inclusive.
2. Diagnosis of systemic lupus erythematosus according to American College of Rheumatology criteria (1997).
3. Active, biopsy-proven proliferative lupus nephritis Class III or IV with/without the presence of Class V, or pure Class V according to the 2003 ISN/RPS classification. The renal biopsy must be performed within 1 year prior to the screening visit or during screening period. The biopsy report will be used to confirm subject eligibility.
4. Positive serum antibody results, defined as positive anti-nuclear antibody (ANA) and/or a positive anti-dsDNA serum antibody based on the study's central laboratory results.
5. Active renal disease at screening requiring induction therapy with high dose corticosteroids (HDCS) with mycophenolate mofetil (MMF) or other oral forms of mycophenolate.
6. Induction therapy for active renal disease: HDCS with mycophenolate mofetil (MMF) or other oral forms of mycophenolate should be initiated within 60 days prior to or on Day 1 (baseline). Initiation of induction is when both HDCS and MMF have been started.
7. Able to understand the requirements of the study and provide written informed consent.

Main Exclusion Criteria:

1. Known hypersensitivity or contraindication to any drug products they plan to receive (e.g., MMF, corticosteroids).

2. History of allergy to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.

3. Received any of the following therapies:

   1. Treatment with any B cell targeted therapy (e.g., rituximab), unless it can be shown that B cells have returned to baseline level or normal;
   2. Received tumor necrosis factor inhibitors, interleukin receptor blockers, or other small molecules or biologics (including Belimumab) during the 12 weeks prior to screening or the 5 half-lives of the drug, whichever is longer;
   3. Received any experimental drugs during the 12 weeks prior to screening or the 5 half-lives of the drug, whichever is longer;
   4. Received plasma separation or plasma exchange during the 6 weeks prior to screening;
   5. Subjects who required dialysis within 1 year prior to screening.
   6. Received a live vaccine or live-attenuated vaccine within 4 weeks prior to screening or expected to vaccinate during the study.
   7. Received BCG Vaccine within 1 year prior to screening.

4. History of severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis) requiring intervention within 60 days of baseline (Day 1).

5. History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant or are due to receive transplantation.

6. Significant, unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.

7. Plan to undergo surgery or have any medical disease, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study.

8. History of drug or alcohol abuse or dependence within 364 days prior to baseline (Day 1).

9. Nursing or pregnant female, or male or female who prepared for parenthood during the study.

10. History of malignant tumors within the last 5 years, excluding adequately treated skin cancer (basal or squamous cell) or carcinoma in situ of cervix.

11. Have acute or chronic infection requiring treatment.

12. HIV positive.

13. Hepatitis B: Patients positive for HBsAg are excluded; Patients negative for HBsAg but positive for Anti-HBc, regardless of Anti-HBs antibody status, will require test for HBV DNA: if HBV DNA positive, patients will be excluded; if HBV DNA negative, patients will be eligible to enroll.

14. Hepatitis C antibody positive.

15. History of COVID-19 within 4 weeks prior to screening or history of hospitalization due to severe Covid-19 within 12 months prior to screening.

16. eGFR<30 mL/min/1.73 m2 using CKD-EPI.

17. Renal biopsy showed 50% glomerulosclerosis.

18. Have a Grade 3 or greater laboratory abnormality based on the Adverse Event Severity Grading Tables.

19. Subjects who in the opinion of the investigator are not suitable to participate.