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

A Multicenter, Randomized, Controlled, Open Phase Ib/ Ⅱ Study Evaluating the Efficacy and Safety of Recombinant Humanized Monoclonal Antibody MIL62 Injection in the Treatment of Primary Membranous Nephropathy.

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.

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