A Study to Assess Effectiveness and Safety of Efgartigimod in Chinese Patients With Lupus Nephritis (ZL-1103-013)

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy and safety of efgartigimod IV in Chinese patients with active lupus nephritis (LN)

Detailed Description
-----------------
To evaluate the efficacy and safety of efgartigimod IV in Chinese patients with active lupus nephritis (LN). The study comprises a maximum 4-week screening period, a 24-week treatment period, and an 8-week follow-up period.

Official Title
-----------------
A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Proof-of-Concept Study to Evaluate the Efficacy and Safety of Efgartigimod in Chinese Patients With Lupus Nephritis

Conditions
-----------------
Lupus Nephritis

Intervention / Treatment
-----------------
* Biological: efgartigimod IV
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥18 years when signing the informed consent form (ICF) Capable of providing signed informed consent, and complying with protocol requirements Diagnosis of SLE according to the Systemic Lupus Erythematosus International Collaborating Clinic (SLICC) 2012 classification criteria Active, proliferative LN Class III or IV [excluding Class III (C), IV-S (C), and IV-G (C)], either with or without the presence of Class V using the 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) criteria, proven by kidney biopsy within 6 months before randomization and confirmed by the central biopsy reading group Require LN induction therapy (glucocorticoids and MMF/MPA) based on investigator's clinical judgment. Induction therapy may begin before screening but should be initiated within 60 days before randomization Agree to use contraceptives consistent with local regulations. Full inclusion criteria can be found in the protocol Exclusion Criteria: Active or chronic infection requiring treatment Any evidence of central nervous system lupus (including but not limited to seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis) Currently on renal dialysis or expected to require dialysis during study period Previous kidney transplantation or planned transplantation during study period History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before randomization. Heart failure due to Systemic Lupus Erythematodes, or any other severe cardiovascular involvement with safety concerns according to investigator's judgment Any other known autoimmune disease that would interfere with an accurate assessment of clinical symptoms of SLE/LN or put the participant at undue risk Previously failed treatment with MMF or any form of mycophenolate-based induction therapy, based on the investigator's opinion Use of complementary therapies, including Traditional Chinese Medicine, herbs, or procedure (eg, acupuncture) that can potentially interfere with the efficacy and safety of participants as assessed by the investigator Received live/live-attenuated vaccine within 28 days before randomization. The receipt of any inactivated, subunit, polysaccharide, or conjugate vaccine at any time before screening is not considered exclusionary. It is recommended that participants are up to date with vaccination(s) before the first dose of IMP Previously participated in a clinical study with efgartigimod SARS-CoV-2 antigen-based positive test at screening. The test is required regardless of whether the participant has been vaccinated Known hypersensitivity or contraindication to efgartigimod, any excipient of the IMP, or SoC medication used in the study In the opinion of the investigator, current or history of (ie, within 12 months of randomization) alcohol, drug, or medication abuse Pregnant or lactating females and those who intend to become pregnant during study participation Any conditions or circumstances that in the opinion of the investigator may make the participant unsuitable for the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efgartigimod IV<br>patients receiving infusions of efgartigimod | Biological: efgartigimod IV<br>* infusion of efgartigimod<br>|
| Placebo Comparator: Placebo<br>patients receiving infusions of placebo | Other: Placebo<br>* infusion of placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 24 in urine protein creatinine ratio (UPCR) |  | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving complete renal response (CRR) at week 24 |  | up to 24 weeks | 
| Time to complete renal response (CRR) |  | up to 32 weeks | 
| Proportion of participants achieving partial renal response at week 24 |  | up to 24 weeks | 
| Time to partial renal response (PRR) |  | up to 24 weeks | 
| Change from baseline to week 24 in estimated glomerular filtration rate (eGFR) |  | up to 24 weeks | 
| Change from baseline to week 24 in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score |  | up to 24 weeks | 
| Change from baseline to week 24 in the dosage of glucocorticoids |  | up to 24 weeks | 
| failure rate during treatment period |  | up to 24 weeks | 
| Proportion of participants achieving modified complete renal response (mCRR) at week 24 |  | up to 24 weeks | 
| Efgartigimod serum concentration-time profile |  | up to 32 weeks | 
| Changes from baseline in levels of total IgG |  | up to 24 weeks | 
| Incidence of ADA against efgartigimod |  | up to 24 weeks | 
| Median changes in concentration from baseline over time in biomarkers (Anti-dsDNA, C3, C4 and CH50) | (all have the same measuring units) | up to 32 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nephritis, Lupus Nephritis, Kidney Disease, Urologic Disease, Glomerulonephritis