A Phase Ⅲ Clinical Study of MIL62 in Primary Membranous Nephropathy

A Phase Ⅲ Clinical Study to Evaluate the Safety and Efficacy of MIL62 Injection in Participants With Primary Membranous Nephropathy

This study will evaluate the efficacy, safety, pharmacokinetics(PK) ,pharmacodynamics（PD）and anti-drug antibodies（ADA） of MIL62 compared with cyclosporine in participants with primary membranous nephropathy (pMN).

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: MIL62; Drug: Cyclosporine

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80;
2. Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening;
3. Screening 24-hour urinary protein >= 5 g after best supportive care for >= 3 months prior to screening or screening Screening 24-hour urinary protein > 3.5 g after best supportive care for >= 6 months prior to screening, or Screening 24-hour urinary protein > 3.5 g with at least one high-risk factor defined by the protocol;
4. Estimated glomerular filtration rate (eGFR ) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ≥40 mL/min/1.73 m^2;
5. If taking ACEI(Angiotensin converting enzyme inhibitors), ARB(Angiotensin receptor blocker), a stable dose within 4 weeks before screening is required;
6. Sufficient organ function;
7. Able and willing to provide written informed consent and to comply with the study protocol.

Exclusion Criteria:

1. Participants with a secondary cause of MN;
2. Cyclosporine resistance;
3. Received treatment drugs for membranous nephropathy;
4. Concomitant with other serious diseases；
5. Received live vaccination, major surgery (excluding diagnostic procedures), and participated in other clinical trials within 28 days prior to receiving the first study drug;
6. Patients who are positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), with HBV DNA levels above the normal range (HBsAg and/or HBcAb-positive patients require regular HBV DNA testing); patients positive for hepatitis C virus (HCV) antibodies; or patients with a positive human immunodeficiency virus (HIV) serology.
7. Participants with CD4+ T lymphocyte count < 200 cells/μL;
8. Those who have a clear history of tuberculosis or have received anti- tuberculosis treatment;
9. Participants with known history of severe allergic reactions to humanized monoclonal antibodies, MIL62, or Cyclosporine
10. Breastfeeding or pregnant women;
11. Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method
12. Other conditions unsuitable for participation in this study determined by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIL62	Drug: MIL62; An intravenous (IV) infusion of 1000 mg of MIL62 will be administered at Week 1 and Week 3.If the treatment is effective, MIL62 will continue be administered at W25 and W27
Active Comparator: Cyclosporine	Drug: Cyclosporine; Participants will receive Cyclosporine at a starting oral dose 3.5 mg/kg/d in 2 divided doses, try to give every 12 hours.The dose was adjusted according to the blood concentration of cyclosporine monitored every 2 weeks±3 days until the target blood concentration of 125~175 ng/mL was reached.Optimized cyclosporine dose will be maintained for a maximum 52 weeks dependent on response and then tapered over 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate at Week 76	The proportion of participants who achieved complete remission (CR) based on Urine Protein-to-Creatinine Ratio (UPCR) at week 76.	Week 76

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission rate at Week 52.	The proportion of participants who achieved CR based on UPCR at week52 (key secondary endpoints)	Week 52
Overall remission rate at Week 52 and 76.	The proportion of participants who achieved overall remission(OR) based on UPCR at week 52 and week76.	Week 52 and 76
Complete remission rate and Overall remission rate at Week 24 and 104.	The proportion of participants who achieved CR and OR based on UPCR at week 24 and week 104.	Week 24 and 104
Complete remission rate and Overall remission rate at Week 24，52，76 and 104.	The proportion of participants who achieved CR or OR as assessed by the Investigators based on 24-hour urine protein at week 24, week 52, week 76 and week 104.	Week 24，52，76 and 104
Time to Treatment Failure or Relapse after Overall remission	Time to Treatment Failure or Relapse after Complete or Partial Remission	Up to 104 weeks
Change in efficacy indicators	Change in anti-PLA2R Autoantibody Titer, UPCR, eGFR, 24-hour urine protein and ALB	Baseline to Week 104
Change in quality of life	Mean Change in T-score from Baseline in the EQ5D Scale at Week 104	Baseline to Week 104
Percentage of Participants with Adverse Events (AEs)	Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	up to 104 weeks
Percentage of Participants with AEs of Special Interest (AESIs)		Up to 104 weeks
Peripheral B-cell Counts at Specified Timepoints		Up to 104 weeks
Serum Concentrations of MIL62 at Specified Timepoints		Up to 104 weeks
Incidence of ADAs during the study		Up to 104 weeks

Collaborators and Investigators

• Sponsor: Beijing Mabworks Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): May 13, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Glomerulonephritis, Membranous; Anti-Infective Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Dermatologic Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: MIL62-CT307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No