A Clinical Study of MIL62 in Primary Membranous Nephropathy

Study Overview
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Brief Summary
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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 was also randomly divided into MIL62 600mg, MIL62 1000mg and cyclosporine groups according to the ratio of 1:1:1, 30 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 76-week overall response rate was the primary endpoint.

Official Title
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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.

Conditions
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Primary Membranous Nephropathy

Intervention / Treatment
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* Drug: MIL62
* Drug: Cyclosporine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, ≥18 years of age; Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening； Best support for 3 months before the screening and above, 24 hours urinary protein 5 g or higher, or screening best support treatment before 6 months or more, 24 hours urinary protein > 3.5 g, and urine protein decreased 50% or less, or if it always has the best support after a full course of treatment, 24 hours urinary protein is still more than standard after confirmed by the researchers can into the group; eGFR ≥40 mL/min/1.73m^2 or qualified endogenous creatinine clearance ≥40 mL/min/1.73m^2 based on 24-hour urine collection during screening； Sufficient organ function; Able and willing to provide written informed consent and to comply with the study protocol. Exclusion Criteria: Participants with a secondary cause of MN； Cyclosporine resistance； Urine protein decreased by > 50% within 6 months before screening； Received treatment drugs for membranous nephropathy； Concomitant with other serious diseases； Received live vaccination, major surgery (other than diagnostic), and participated in other clinical trials within 28 days prior to receiving the first study drug;Central nervous system metastasis； Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C(including HBsAg,HBcAb positive with abnormal HBV DNA or HCV RNA ); Those who have a clear history of tuberculosis or have received anti-tuberculosis treatment； Other exclusion criteria may apply；

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIL62<br> | Drug: MIL62<br>* An intravenous (IV) infusion of 600 mg of MIL62 will be administered at Week 1，Week 3.If the treatment is effective, MIL62 will continue be administered at W25，W27.<br>|
| Active Comparator: Ciclosporin<br> | Drug: Cyclosporine<br>* 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.Cyclophosphamide will be maintained for 12 months, after which the dose was reduced by about 1/3 to 1/2 of the original dose each month, and discontinued after 2 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Percentage of Participants with Adverse Events | Percentage of Participants with AEs and SAEs assessed by NCI CTCAE v5.0. | up to 2year after enrollment | 
| Stage 2: Overall response rate (CR+PR) at Week 76 | Percentage of Participants with complete and partial response as assessed by the investigator. | Week 76 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 2: complete response, partial response, and overall response (CR+PR) at 104 weeks | Percentage of Participants with complete and partial response as assessed by the investigator. | Week 104 | 
| Stage 2: Complete response rate, partial response rate and overall response rate at 24 weeks and 52 weeks (CR+PR) | Percentage of Participants with complete 、partial response as assessed by the investigator. | Week 52 |