A Study of Telitacicept in Lupus Nephritis

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

Detailed Description
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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).

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

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Biological: Telitacicept 240 mg
* Biological: Telitacicept 160 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Males or females aged 18-75 years of age, inclusive. Diagnosis of systemic lupus erythematosus according to American College of Rheumatology criteria (1997). 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. 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. Active renal disease at screening requiring induction therapy with high dose corticosteroids (HDCS) with mycophenolate mofetil (MMF) or other oral forms of mycophenolate. 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. Able to understand the requirements of the study and provide written informed consent. Main Exclusion Criteria: Known hypersensitivity or contraindication to any drug products they plan to receive (e.g., MMF, corticosteroids). History of allergy to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. Received any of the following therapies: 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; 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; Received any experimental drugs during the 12 weeks prior to screening or the 5 half-lives of the drug, whichever is longer; Received plasma separation or plasma exchange during the 6 weeks prior to screening; Subjects who required dialysis within 1 year prior to screening. Received a live vaccine or live-attenuated vaccine within 4 weeks prior to screening or expected to vaccinate during the study. Received BCG Vaccine within 1 year prior to screening. 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). History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant or are due to receive transplantation. 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. 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. History of drug or alcohol abuse or dependence within 364 days prior to baseline (Day 1). Nursing or pregnant female, or male or female who prepared for parenthood during the study. History of malignant tumors within the last 5 years, excluding adequately treated skin cancer (basal or squamous cell) or carcinoma in situ of cervix. Have acute or chronic infection requiring treatment. HIV positive. 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. Hepatitis C antibody positive. 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. eGFR<30 mL/min/1.73 m2 using CKD-EPI. Renal biopsy showed 50% glomerulosclerosis. Subjects who in the opinion of the investigator are not suitable to participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept 240 mg<br>Telitacicept 240 mg given SC weekly plus standard therapy through week 48. | Biological: Telitacicept 240 mg<br>* Participants will receive Telitacicept 240mg weekly in addition to SOC for 48 weeks.<br>* Other names: RC18 240 mg;|
| Experimental: Telitacicept 160 mg<br>Telitacicept 160 mg given SC weekly plus standard therapy through week 48. | Biological: Telitacicept 160 mg<br>* Participants will receive Telitacicept 160mg weekly in addition to SOC for 48 weeks.<br>* Other names: RC18 160 mg;|
| Placebo Comparator: Placebo<br>Placebo given SC weekly plus standard therapy through week 48. | Drug: Placebo<br>* Participants will receive placebo weekly in addition to SOC for 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Complete Renal Response (CRR) | CRR is defined as estimated glomerular filtration rate (GFR) is no more than 20% below the baseline value or ≥ 60 mL/min/1.73m^2 and 24-hour urinary protein: creatinine ratio ≤ 0.5 mg/mg and did not receive prohibited or rescue therapy resulting in treatment failure. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Partial Renal Response (PRR) | PRR is defined as 24-hour urinary protein: creatinine ratio reduced by 50% compared to baseline value. | Week 24 and Week 48 | 
| Incidence of AE, SAE | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A SAE is any untoward medical occurrence that at any dose resulting in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant and which the investigator regards as serious based on appropriate medical judgment. | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus, nephritis, Telitacicept, RC 18