The purpose of this Phase 2 study is to investigate the effect of XmAb5871 on IgG4-Related Disease (RD) activity

Inclusion Criteria:

• Active IgG4-RD
• Compatible pattern of organ involvement consistent with IgG4-RD that cannot be attributed to other causes
• Histopathologically-proven diagnosis of IgG4-RD
• Peripheral blood plasmablast count >900 cells/mL and/or elevated IgG4-RD levels during screening
• Able and willing to complete the entire study according to the study schedule
• Able and willing to provide written informed consent

Exclusion Criteria:

• History or evidence of a clinically unstable/uncontrolled disorder, condition or disease other than IgG4-RD that, in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion
• Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin, or prostate cancer with no recurrence ≥3 years following prostatectomy)
• Presence of recurrent or chronic infections, defined as ≥3 infections requiring antimicrobials over the past 6 months prior to screening
• Active infection requiring hospitalization or treatment with parenteral antimicrobials within the 60 days prior to randomization or oral antimicrobials within the 21 days prior to enrollment
• Patient is taking >40 mg of prednisone QD
• Prior use of rituximab (or other B cell depleting agents) within 6 months of enrollment. Prior use of any B cell depleting agent greater than 6 months from enrollment is allowed if the CD19+ B cell count is within the normal reference range during screening
• Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life is unknown) prior to enrollment
• Immunosuppressive agent use within the three months prior to enrollment
• Has received live vaccines within 2 months of enrollment
• Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to end-of-study visit
• Unable or unwilling to partake in the follow-up assessments or required protocol procedures

Day 1 (First Dose) through Day 197

Note that due to the small total of 20 participants, the frequency threshold for reporting other adverse events applies to the total participants rather than the two defined dosing groups. Specifically, the threshold is adverse events occurring in 2 or more of 20 total participants (i.e. > 5% of 20).

The fixed-dose group was added by amendment to collect information on fixed IV doses with bioequivalence to subcutaneous doses planned for future studies. This group is not intended for efficacy or safety comparisons to the initial 15 participants.