This study is a multicenter, randomized, controlled, open-label, Phase Ⅱ clinical study to evaluate the efficacy, safety, Pharmacokinetics characteristics, Pharmacodynamics effects, and immunogenicity of JMT601 in participants with primary membranous nephropathy.

The study has two parts. Part one is dose escalation part, and Part two is dose expansion part.

Inclusion Criteria:

1. The age range is between 18 and 80 years old, regardless of gender.
2. Diagnosed with primary membranous nephropathy by renal biopsy during the screening/induction period or within 24 months before screening. Pathological reports must be reviewed by the investigator prior to study drug administration.
3. The glomerular filtration rate (eGFR) estimated by CKD-EPI formula is ≥ 40ml/min/1.73m^2, or the endogenous creatinine clearance rate (CrCl) based on 24-hour urine examination is ≥ 40ml/min.
4. Participants taking angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists must maintain a stable dose for at least 4 weeks before screening;
5. Participants with systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening.
6. During the screening period and the baseline visit, the 24-hour urine protein is > 3.5g.
7. Have never received immunosuppressive therapy for PMN (cyclophosphamide, calcineurin inhibitors, such as cyclosporine and tacrolimus) and B cell exhaustion therapy (such as rituximab); or relapsed after receiving the above treatment to achieve complete remission or partial remission (comprehensively judged and recorded by the researcher), and have not received the above treatment after recurrence (excluding those who are ineffective or resistant to B cell depletion drugs).
8. Have fully understood this study and voluntarily signed the informed consent form.

Exclusion Criteria:

1. Secondary membranous nephropathy.

2. Diagnostic renal biopsy shows evidence of glomerular crescent formation, which suggests the diagnosis of other renal diseases or renal biopsy evidence of interstitial fibrosis/tubular atrophy in cortical area > 50%.

3. Uncontrolled blood pressure as judged by the investigator within the 3 months prior to screening.

4. Individuals with evidence of a ≥50% decrease in urine protein within the first 6 months before screening.

5. Currently undergoing or planning to undergo renal replacement therapy during the study period.

6. Type 1 diabetes or type 2 diabetes with diabetic nephropathy (confirmed by renal biopsy report) or without biopsy-confirmed diabetic nephropathy but with a diabetes duration ≥5 years.

7. Presence of severe, progressive, or uncontrolled comorbidities.

8. Individuals who have had or currently have malignant tumors.

9. Participants with autoimmune diseases requiring systemic immunosuppression therapy, or those judged by researchers to have autoimmune diseases that interfere with the clinical evaluation of primary membranous nephropathy or are not suitable for clinical trials.

10. A history of previous or current hemolytic anemia, Evans syndrome, arteritis.

11. Participants with suspected active or latent tuberculosis patients based on medical history or tuberculosis screening.

12. Severe active bacterial, viral, fungal, mycobacterial, parasitic, or other infections requiring systemic antibiotics or antiviral treatment within 1 month before screening.

13. Have received prescribed treatment for membranous nephropathy before screening.

14. Participants using of complementary therapies that may interfere with the investigator's assessment of participant efficacy and safety within 4 weeks prior to randomization.

15. Live vaccines or major surgery within 28 days before the investigational drug administration or undergoing major surgery.

16. Participants who have participated in clinical trials of other drugs with a screening time less than 30 days from the last administration or the five half-lives of the original drug (whichever is longer), or those who plan to participate in clinical trials of another drug during the study period.

17. Participants who have received targeted CD47 or signal regulatory protein α (SIRPα) therapy.

18. A history of alcoholism or drug abuse within 12 months.

19. Virology test results at screening meet the criteria:

    HBsAg positivity; If HBsAg is negative and HBcAb is positive, HBV DNA should be exceeding the upper limit of the local laboratory reference range; Positive hepatitis C virus (HCV) antibody with detectable HCV RNA; Positive serology for human immunodeficiency virus (HIV).

20. Any of the following abnormal laboratory test results during screening: hemoglobin<80g/L, platelet count<100× 10^9/L , absolute neutrophil count<1.5× 10^9/L , AST or ALT values>2× upper limit of normal (ULN), CD4+ T lymphocyte count < 300 cells/μL, QTcF>450 ms for males and >460 ms for females.

21. Participants who have previously shown resistance to CD20 inhibitors or cyclosporine.

22. Known history of severe hypersensitivity reactions to humanized monoclonal antibodies or documented allergy to any component of rituximab (dose-escalation part only), JMT601 injection, or cyclosporine (dose-expansion part only).

23. Pregnant or lactating women; Women of childbearing potential not undergoing sterilization who are unwilling to use adequate contraception during treatment and for at least 6 months after the last dose of the investigational drug.

24. Men not undergoing sterilization who are unwilling to use barrier contraception during the study and for at least 6 months after the last dose of the investigational drug, and who refuse to ensure their partners use additional contraceptive methods (e.g., oral contraceptives, intrauterine devices, barrier methods, or spermicides).

25. Other conditions that the investigator deems render the subject unsuitable for study participation.