A Study to Assess Effectiveness and Safety of Efgartigimod in Chinese Patients With Primary Membranous Nephropathy (ZL-1103-014)

Membranous Nephropathy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05810961
• Other study ID #: ARGX-113-2203
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2023
• Est. completion date: October 2024

Study information

• Verified date: March 2024
• Source: argenx
• Contact: Sabine Coppieters, MD
• Phone: 857-350-4834
• Email: clinicaltrials[@]argenx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: October 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Membranous Nephropathy

Intervention

Biological:
• efgartigimod IV
infusion of efgartigimod

Other:
• placebo
infusion of placebo

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing
China	Hunan Provincial People's Hospital	Changsha
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	Fujian Medical University Union Hospital	Fujian
China	Fuyang People's Hospital	Fuyang
China	Guangdong Provincial People's Hospital	Guangzhou
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou
China	The First Affiliated Hospital, Sun Yat-sen University	Guanzhou
China	The First Affiliated Hospital, Zhejiang University	Hanzhou
China	The Second Hospital of Anhui Medical University	Hefei
China	The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University	Huai'an
China	Shandong Provincial Hospital Affiliated to Shandong First Medical University	Jinan
China	Liu Zhou Works Hospital	Liuzhou
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Zhongda Hospital Southeast University	Nanjing
China	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning
China	Pingxiang People's Hospital	Pingxiang
China	Huashan Hospital Fudan University	Shanghai
China	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai
China	ShengJing Hospital of China Medical University	Shenyang
China	Shenzhen People's Hospital	Shenzhen
China	The First Hospital of Hebei Medical University	Shijia Zhuang
China	The Second Hospital of Tianjin Medical University	Tianjin
China	Renmin Hospital of Wuhan University	Wuhan
China	Wuxi People's Hospital	Wuxi
China	Shaanxi Provincial Hospital of Chinese Medicine	Xi'an
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	Xiamen Fifth Hospital	Xiamen
China	Henan Provincial People's Hospital	Zhengzhou
China	Zhuhai People's Hospital	Zhuhai

Sponsors (2)

Lead Sponsor	Collaborator
argenx	Zai Lab Pty. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to week 24 in urine protein creatinine ratio (UPCR) in anti- PLA2R antibody (Ab) seropositive population		up to 24 weeks
Secondary	Change from baseline to week 24 in urine protein creatinine ratio (UPCR) in overall population		up to 24 weeks
Secondary	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		up to 24 weeks
Secondary	Time to complete remission (CR) in overall population and anti-PLA2R Ab seropositive population		up to 32 weeks
Secondary	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		up to 24 weeks
Secondary	Time to partial remission (PR) in overall population and anti-PLA2R Ab seropositive population		up to 32 weeks
Secondary	Change from baseline to week 24 in anti-PLA2R Ab in anti-PLA2R Ab seropositive population		up to 24 weeks
Secondary	Change from baseline to week 24 in serum albumin in overall population and anti-PLA2R Ab seropositive population		up to 24 weeks
Secondary	Change from baseline to week 24 in estimated glomerular filtration rate (eGFR) in overall population and anti-PLA2R Ab seropositive population		up to 24 weeks
Secondary	Treatment failure rate during treatment period in overall population and anti-PLA2R Ab seropositive population		up to 32 weeks
Secondary	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		up to 32 weeks
Secondary	Efgartigimod serum concentration-time profile in overall population and anti-PLA2R Ab seropositive population		up to 32 weeks
Secondary	changes from baseline in levels of total IgG		up to 32 weeks
Secondary	Incidence of antidrug antibodies (ADA) against efgartigimod in overall population and anti-PLA2R Ab seropositive population		up to 32 weeks
Secondary	Change from baseline in EQ5D-5L score in overall population and anti-PLA2R Ab seropositive population		up to 24 weeks
Secondary	Change from baseline in PROMIS Short form v1.0 Fatigue-4a questionnaire in overall population and anti-PLA2R Ab seropositive population		up to 24 weeks