Inclusion Criteria:

• Signed Informed Consent Form.
• Age 18-75 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol, in the investigator's judgment.
• Active or active/chronic ISN/RPS 2003 Class III or IV proliferative LN by renal biopsy performed in the 6 months prior to screening or during screening:
  • One or more active glomerular lesions must be present;
  • Class V disease may be present in addition to Class III or IV;
  • The local biopsy report will be used to determine eligibility.
• SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria, which are met by the presence of Class III or IV LN (above) and current or past positive antinuclear antibody (ANA) Positive ANA is defined by ANA at a titer of ≥ 1:80 on HEp-2 cells or an equivalent positive ANA test at least once. UPCR ≥ 1 on a 24-hour collection at screening
• Receipt of at least one dose of pulse methylprednisolone IV (≥ 250 mg) or equivalent for treatment of the current episode of active LN during the 6 months prior to screening or during screening, or to be given on Day 1 prior to the first infusion.
  • A maximum of 3 g methylprednisolone IV or equivalent during the 4 weeks prior to screening or during screening is allowed.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraception, as defined below: Women must remain abstinent or use two reliable methods of contraception, including at least one method with a failure rate of < 1% per year, during study treatment and for 18 months after the final dose of obinutuzumab or placebo and 6 weeks after the final dose of MMF. 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. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation; male sterilization; established, proper use of hormonal contraceptives that inhibit ovulation; hormone-releasing intrauterine devices; and copper intrauterine devices. 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: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method used by the female partner that together result in a failure rate of < 1% per year during the treatment period and for 90 days after the final dose of MMF. Men must refrain from donating sperm during this same period. 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.

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF.
• Women of childbearing potential, including those who have had a tubal ligation, must have a negative urine pregnancy test at screening. Positive test results will be confirmed with a serum pregnancy test. Severe renal impairment, as defined by eGFR < 30 mL/min/1.73 m^2 (as estimated using the CKD-EPI equation) or the need for dialysis or renal transplantation.
• Sclerosis in > 50% of glomeruli on renal biopsy.
• Presence of rapidly progressive glomerulonephritis, defined by any of the following:
  • Crescent formation in ≥ 50% of glomeruli assessed on renal biopsy;
  • Sustained doubling of serum creatinine during the 2 months prior to screening;
  • The investigator’s opinion that the patient has rapidly progressive glomerulonephritis.
• Receipt of any of the following excluded therapies:
  • Any anti-CD20 therapy such as rituximab, ocrelizumab, or ofatumumab less than 9 months prior to screening or during screening;
  • If an anti-CD20 therapy has been received between 9 and 12 months prior to screening, the peripheral CD19+ B-cell count must be ≥ 25 cells/µL;
  • Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening;
  • Any biologic therapy (other than anti-CD20) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening;
  • Oral inhibitors of Janus-associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening;
  • Any live vaccine during the 28 days prior to screening or during screening.
• Severe, active central nervous system SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia.
• High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions.
• Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation.
• HIV infection:
  • For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations.
• 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.
• Active infection of any kind, excluding fungal infection of the nail beds.
• Any major episode of infection that also fulfills any of the following criteria:
  • Requires hospitalization during the 8 weeks prior to screening or during screening;
  • Requires treatment with IV antibiotics or anti-infectives during the 8 weeks prior to screening or during screening;
  • Requires treatment with oral antibiotics or anti-infectives during the 2 weeks prior to screening or during screening:
    • Antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary.
• 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, within the past 5 years:
  • Patients with non-melanomatous carcinomas of the skin that have been treated or excised and have resolved are eligible.
• Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening.
• Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening.
• Intolerance or contraindication to study therapies, including any of the following:
  • 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;
  • Intolerance to MMF;
  • Lack of peripheral venous access.
• Any of the following laboratory parameters:
  • AST or ALT > 2.5 x ULN;
  • Amylase or lipase > 2 x ULN;
  • Neutrophils < 1.5 x10^3 /µL;
  • Positive hepatitis B surface antigen (HBsAg);
  • Patients who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
• Positive hepatitis C serology Patients with positive hepatitis C antibody test result with no detectable hepatitis C virus (HCV) RNA at least 6 months after completion of antiviral therapy are eligible but will require monthly HCV RNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
• Hemoglobin < 7 g/dL, unless caused by autoimmune hemolytic anemia resulting from SLE.
• Platelet count < 25,000/µL.
• Positive serum human chorionic gonadotropin measured at screening.

Eligibility last updated 9/9/21. Questions regarding updates should be directed to the study team contact.