Primary Membranous Nephropathy
Conditions
Brief summary
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).
Interventions
DRUGMIL62
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
DRUGCyclosporine
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.
Sponsors
Beijing Mabworks Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate at Week 76 | Week 76 | The proportion of participants who achieved complete remission (CR) based on Urine Protein-to-Creatinine Ratio (UPCR) at week 76. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate and Overall remission rate at Week 24，52，76 and 104. | 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. |
| Complete Remission rate at Week 52. | Week 52 | The proportion of participants who achieved CR based on UPCR at week52 (key secondary endpoints) |
| Overall remission rate at Week 52 and 76. | Week 52 and 76 | The proportion of participants who achieved overall remission(OR) based on UPCR at week 52 and week76. |
| Time to Treatment Failure or Relapse after Overall remission | Up to 104 weeks | Time to Treatment Failure or Relapse after Complete or Partial Remission |
| Change in efficacy indicators | Baseline to Week 104 | Change in anti-PLA2R Autoantibody Titer, UPCR, eGFR, 24-hour urine protein and ALB |
| Complete remission rate and Overall remission rate at Week 24 and 104. | Week 24 and 104 | The proportion of participants who achieved CR and OR based on UPCR at week 24 and week 104. |
| Percentage of Participants with Adverse Events (AEs) | up to 104 weeks | Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 |
| 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 | — |
| Change in quality of life | Baseline to Week 104 | Mean Change in T-score from Baseline in the EQ5D Scale at Week 104 |
Countries
China
Outcome results
None listed