Clinical trial NCT05810961: A Study to Assess Effectiveness and Safety of Efgartigimod in Chinese Patients with Primary Membranous Nephropathy (ZL-1103-014)
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 Primary Membranous Nephropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Membranous Nephropathy
Keywords: kidney disease
Glomerulonephritis membranous
Urologic disease
glomerulonephritis
Lead sponsor: argenx
Sponsor class: INDUSTRY
Collaborators: name: Zai Lab Pty. Ltd.
First posted: 2023-04-13
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of efgartigimod IV in Chinese patients with primary membranous nephropathy (pMN).

Detailed description: To evaluate the efficacy and safety of efgartigimod IV in Chinese patients with primary membranous nephropathy (pMN).The study comprises a maximum 4-week screening period, a 24-week treatment period, and an 8-week follow-up period

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 idiopathic (primary) MN confirmed by renal biopsy within 24 months before randomization. A renal biopsy may be taken at any time during the screening period to confirm the diagnosis of MN for participant eligibility, if the most recent biopsy was performed greater than 24 months before randomization
* Receiving stable dose at maximum tolerated or allowed dose of ACEi and/or ARB for at least 12 weeks 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
* Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive of an alternative or additional diagnosis to pMN; evidence on renal biopsy of \>50% interstitial fibrosis/tubular atrophy in the cortical area
* History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before randomization.
* Any evidence of diabetic glomerulopathy on renal biopsy that is:

Greater than Class I diabetic glomerulopathy, or Class I diabetic glomerulopathy with a history of poor diabetic control (eg, HbA1c ≥9.0%) since time of biopsy

* Currently on renal dialysis or expected to require dialysis during study period
* Previous kidney transplantation or planned transplantation during study period
* Any other known autoimmune disease that, requires systemic immunosuppressive treatments, or in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of pMN or put the participant at undue risk
* Clinical evidence of other significant or uncontrolled serious diseases (ie, cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological), have had a recent major surgery, or have any other condition, that in the opinion of the investigator, could confound the results of the study or put the participant at undue risk
* Use of complementary therapies, including Traditional Chinese Medicine, herbs, or procedures (eg, acupuncture) within 4 weeks before randomization 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 screenings is not considered exclusionary. It is recommended that participants are up to date with vaccination before the first dose of IMP
* Previously participated in a clinical study with efgartigimod
* SARS-CoV-2 positive test at screening. The test is required regardless of whether the participant has been vaccinated
* Known hypersensitivity or contraindication to efgartigimod, or any excipient of the IMP
* 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

Primary outcomes:
measure: Change from baseline to week 24 in urine protein creatinine ratio (UPCR) in anti- PLA2R antibody (Ab) seropositive population
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Change from baseline to week 24 in urine protein creatinine ratio (UPCR) in overall population
timeFrame: up to 24 weeks
measure: Proportion of participants achieving complete remission (CR), defined as proteinuria ≤0.3g/24-hour and serum albumin ≥3.5g/dL, at week 24 in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Time to complete remission (CR) in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: Proportion of participants achieving partial remission (PR), defined as ≥50% reduction in proteinuria from baseline AND final proteinuria between 0.3 to 3.5g/24-hour, at week 24 in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Time to partial remission (PR) in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: Change from baseline to week 24 in anti-PLA2R Ab in anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Change from baseline to week 24 in serum albumin in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Change from baseline to week 24 in estimated glomerular filtration rate (eGFR) in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Treatment failure rate during treatment period in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: Incidence of relapse, defined as the development of nephrotic range proteinuria following CR or PR, ie, >3.5g/24-hour throughout the study in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: Efgartigimod serum concentration-time profile in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: changes from baseline in levels of total IgG
timeFrame: up to 32 weeks
measure: Incidence of antidrug antibodies (ADA) against efgartigimod in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 32 weeks
measure: Change from baseline in EQ5D-5L score in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
measure: Change from baseline in PROMIS Short form v1.0 Fatigue-4a questionnaire in overall population and anti-PLA2R Ab seropositive population
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Fujian
country: China
facility: Fujian Medical University Union Hospital
city: Fuyang
country: China
facility: Fuyang People's Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guanzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Hanzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Huai'an
country: China
facility: The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University
city: Jinan
country: China
facility: Shandong Provincial Hospital Affiliated to Shandong First Medical University
city: Liuzhou
country: China
facility: Liu Zhou Works Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine
city: Shenyang
country: China
facility: ShengJing Hospital of China Medical University
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Shijia Zhuang
country: China
facility: The First Hospital of Hebei Medical University
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Wuxi
country: China
facility: Wuxi People's Hospital
city: Xi'an
country: China
facility: Shaanxi Provincial Hospital of Chinese Medicine
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Xiamen Fifth Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhuhai
country: China
facility: Zhuhai People's Hospital
Study officials:
References: