Inclusion Criteria:

• Signed Informed Consent Form.
• Age 18 to 75 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol, in the investigator's judgment.
• Diagnosis of pMN according to renal biopsy prior to or during screening.
  • Diagnosis should be based on light and immunofluorescence microscopy, and if possible, electron microscopy.
• UPCR ≥ 5 g from 24-hour urine collection despite best supportive care for ≥ 3 months prior to screening or UPCR ≥ 4 g despite best supportive care ≥ 6 months prior to screening.
  • Best supportive care comprises renin-angiotensin system blockade with ACE inhibitor and/or ARB at maximally tolerated approved dose.
• Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening
• eGFR ≥ 40 mL/min/1.73m^2 or qualified endogenous creatinine clearance ≥ 40 mL/min based on 24-hour urine collection during screening. eGFR is calculated using the CKD-EPI equation (Levey, et al. 2009).
• Patients who previously responded to CNIs (CsA or tacrolimus), rituximab, or alkylating agents with either a CR or PR and subsequently relapsed are eligible but require discontinuation of CNIs or alkylating agents for ≥ 6 months and rituximab for ≥ 9 months prior to screening.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 18 months after the final dose of obinutuzumab and for 28 days after the final dose of tacrolimus.
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
  • The following are examples of adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormone-releasing intrauterine devices; copper intrauterine devices; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For men receiving tacrolimus:  agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, as defined below:
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.
  • With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 28 days after the final dose of tacrolimus to avoid exposing the embryo.
  • For patients enrolled in the extended China enrollment phase at NMPA-recognized sites: current resident of mainland China and of Chinese ancestry.

Exclusion Criteria:

• Patients with a secondary cause of MN (e.g., hepatitis B, SLE, medications, malignancies).
• Uncontrolled blood pressure, in the opinion of the investigator, during 3 months prior to screening.
• Evidence of ≥  50% reduction in proteinuria during the previous 6 months prior to randomization.
• Receipt of renal replacement therapy (e.g., renal transplantation, chronic dialysis).
• Type 1 or 2 diabetes mellitus (to exclude proteinuria secondary to diabetic nephropathy).
• Patients who have recent history of steroid-induced diabetes but no evidence on renal biopsy for diabetic nephropathy performed within 6 months of entry into the study are eligible.
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or 28 days after the final dose of tacrolimus.
• Women of childbearing potential, including those who have had a tubal ligation, must have a negative pregnancy test result within 1 day prior to each obinutuzumab infusion.
• History of resistance (no response) to CNIs or B-cell depleting antibodies.
• Patients with non-response to rituximab due to development of human anti-chimeric antibodies will be eligible.
• Receipt of previous therapies as follows:
  • Treatment with MMF or oral, intramuscular, or intravenous corticosteroids within 1 month prior to screening;
  • Any B-cell depleting therapy such as rituximab, ocrelizumab, or ofatumumab within 9 months prior to screening;
  • Treatment with cyclophosphamide or CNI within 6 months prior to screening;
  • Treatment with any biologic therapy (other than B-cell depleting agents) such as belimumab, ustekinumab, or anifrolumab (investigational) within 6 months prior to screening;
  • Treatment with an inhibitor of Janus-associated kinase, Bruton’s tyrosine kinase, or tyrosine kinase 2, including but not limited to tofacitinib, baricitinib, upadacitinib, filgotinib (investigational), ibrutinib, or fenebrutinib (investigational) within 3 months prior to screening;
  • Treatment with any investigational agent within 28 days of screening or 5 drug-elimination half-lives of the investigational drug, whichever is longer;
  • Receipt of a live vaccine within 28 days prior to screening or during screening.
• Thrombocytopenia, anemia, and/or coagulopathy with high risk for clinically significant bleeding or organ dysfunction or requiring plasmapheresis, IVIg, or acute blood product transfusions.
• Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation.
• Known HIV infection. 
• Tuberculosis (TB) infection:
  •  Testing for latent TB will be performed at screening if required by local regulations or in accordance with local clinical practice;
  •  Latent TB after completion of appropriate treatment is not exclusionary.
• Known active infection of any kind, excluding fungal infection of the nail beds.
• Any major episode of infection requiring hospitalization or treatment either with IV anti-infective treatments during the 2 months prior to or during screening or with oral anti-infective treatments during the 2 weeks prior to or during screening.
• History of serious recurrent or chronic infection.
• History of progressive multifocal leukoencephalopathy (PML).
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, except non-melanomatous carcinomas of the skin that have been treated or excised and have resolved.
• Major surgery requiring hospitalization within the 4 weeks prior to screening.
• Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening.
• Intolerance or contraindication to study therapies, including:
  • Evidence of intolerance or toxicity associated with tacrolimus prior to screening;
  • History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion;
  • Intolerance or contraindication to oral or IV corticosteroids and premedications;
  • Intolerance or hypersensitivity to tacrolimus and its excipients;
  • Lack of peripheral venous access. 
• Laboratory parameters:
  • AST or ALT 2.5 > the upper limit of normal (ULN);
  • Amylase or lipase > 2 x ULN;
  • Neutrophils < 1.5 x 10^3 /µL;
  • CD19+ B cells < 5/µL;
  • Positive for hepatitis B surface antigen (HBsAg) at screening.
  • Patients who are HBsAg negative and hepatitis B core antibody positive with no detectable hepatitis B virus (HBV) DNA will be allowed into the study but will require regular HBV DNA monitoring;
  • Positive hepatitis C virus (HCV) antibody at screening.
  • Patients with positive hepatitis C antibody test result with no detectable HCV RNA for at least 12 months after completion of antiviral therapy are eligible but will require regular HCV RNA monitoring;
  • Hemoglobin < 9 g/dL;
  • Platelet count < 75,000/µL;
  • Positive serum human chorionic gonadotropin measured at screening.

Eligibility last updated 12/2/21. Questions regarding updates should be directed to the study team contact.