A Phase Ib/ Ⅱ Clinical Study of MIL62 in Primary Membranous Nephropathy

NCT ID: NCT05398653

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-24
• Study Completion Date: 2025-04-18

Brief Summary

This study was divided into two stages. In the first stage (Phase Ib), 30 subjects were randomly divided into MIL62 600mg, MIL62 1000mg and cyclosporine groups at a ratio of 1:1:1, with 10 subjects in each group. Tolerance to MIL62 was evaluated within 4 weeks after the first administration. If the overall safety is determined by the investigator and sponsor to be tolerable to MIL62, phase II enrollment will be initiated.

The second stage(Phase II) was also randomly divided into MIL62 600mg, MIL62 1000mg and cyclosporine groups according to the ratio of 1:1:1, 20 subjects in each group, to evaluate the efficacy of MIL62 and cyclosporine in the treatment of primary membranous nephropathy. Eligible subjects in both phases received treatment and follow-up for a total of 104 weeks. The primary efficacy endpoints were the 12-week immune remission rate and the 24-week overall remission rate.

Conditions

Primary Membranous Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MIL62(600mg)

Group Type: EXPERIMENTAL

MIL62

Intervention Type: DRUG

A 600 mg intravenous (IV) infusion of MIL62 will be administered on Week 1 Day 1 and Week 3 Day 1. If treatment response is observed, additional doses will be administered on Week 25 Day 1 and Week 27 Day 1. According to the protocol amendment in June 2023, some patients also received MIL62 treatment on Week 53 Day 1.

Ciclosporin

Group Type: ACTIVE_COMPARATOR

Cyclosporine

Intervention Type: DRUG

Participants will receive Cyclosporine at a starting oral dose 3.5 mg/kg/d, divided into 2 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.

MIL62(1000mg)

Group Type: EXPERIMENTAL

MIL62

Intervention Type: DRUG

A 1000 mg intravenous (IV) infusion of MIL62 will be administered on Week 1 Day 1 and Week 3 Day 1. If treatment response is observed, additional doses will be administered on Week 25 Day 1 and Week 27 Day 1. According to the protocol amendment in June 2023, some patients also received MIL62 treatment on Week 53 Day 1.

Interventions

MIL62

A 600 mg intravenous (IV) infusion of MIL62 will be administered on Week 1 Day 1 and Week 3 Day 1. If treatment response is observed, additional doses will be administered on Week 25 Day 1 and Week 27 Day 1. According to the protocol amendment in June 2023, some patients also received MIL62 treatment on Week 53 Day 1.

Intervention Type: DRUG

Cyclosporine

Participants will receive Cyclosporine at a starting oral dose 3.5 mg/kg/d, divided into 2 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.

Intervention Type: DRUG

MIL62

A 1000 mg intravenous (IV) infusion of MIL62 will be administered on Week 1 Day 1 and Week 3 Day 1. If treatment response is observed, additional doses will be administered on Week 25 Day 1 and Week 27 Day 1. According to the protocol amendment in June 2023, some patients also received MIL62 treatment on Week 53 Day 1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult patients, ≥18 years of age;

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 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. Sufficient organ function;

6. 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. Urine protein decreased by > 50% within 6 months before screening

4. Received treatment drugs for membranous nephropathy

5. Concomitant with other serious diseases

6. Received live vaccination, major surgery (excluding diagnostic procedures), and participated in other clinical trials within 28 days prior to receiving the first study drug

7. 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

8. Participants with CD4+ T lymphocyte count < 300 cells/μL

9. Those who have a clear history of tuberculosis or have received anti- tuberculosis treatment

10. Participants with known history of severe allergic reactions to humanized monoclonal antibodies, MIL62, or Cyclosporine

11. Breastfeeding or pregnant women

12. Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method

13. Other conditions unsuitable for participation in this study determined by the Investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Mabworks Biotech Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

MIL62-CT206

Identifier Type: -

Identifier Source: org_study_id