This is a Phase 2, single center, proof of concept clinical trial in subjects with active IgG4-Related Disease (IgG4-RD). Approximately 10 subjects with active IgG4-RD will be enrolled into this study. Subjects will receive weekly subcutaneous doses of abatacept (125mg) for 24 doses (24 weeks).

After obtaining informed consent, all screening procedures and tests establishing eligibility will be performed on the initial screening visit. Subjects determined to be eligible at screening will receive an initial subcutaneous dose of abatacept (125mg), which will be continued weekly for a total of up to 24 doses (24 weeks). Steroid therapy must be tapered off and discontinued over a 4 week period (taper must be completed no later than week 4). Should patients be deemed to have worsening disease or failing therapy at 4 weeks then a trial of steroids can be considered.

Subjects will return on weeks 1, 2, 4, 8, 12, 16, 20, and 24 while on treatment for their injections, and for the scheduled safety and disease response assessments. Subjects will be allowed to self-administer their injections at home. The full treatment period is 24 doses given weekly for 24 weeks. Subjects who are not able to be tapered off corticosteroids or who require reinstitution of corticosteroid therapy at any time during the study will be counted as treatment failures, but may continue on study. Should the IgG4-RD responder index fail to improve by 8 weeks or should there be development of new organ failure at 4 weeks, patient's will be deemed treatment failure and can begin corticosteroid or alternative immunosuppressive therapy at the Investigator's discretion. Those who require rituximab or who require addition of other oral immunosuppressives will be counted as treatment failures and will terminate the study.

All subjects completing the treatment period will have follow up visits off protocolized treatment at 28 and 36 weeks. All adverse events (including serious adverse events (AEs) and deaths) and use of concomitant medication information will be collected throughout the study from screening through study termination. Subjects developing treatment-emergent adverse events or clinically significant safety lab abnormalities will be followed until resolution or until stabilization of the adverse events/abnormalities.

Inclusion Criteria:

1. Are male or female 18 years of age or older
2. Meet the American College of Rheumatology (ACR)/EULAR 2018 Classification Criteria for IgG4-RD
3. Have active disease based on an IgG4-RD Responder Index (RI) ≥2 at screening with disease manifestation in at least one organ system excluding lymph nodes at screening
4. May or may not have received prior IgG4-RD therapy
5. Must be willing to taper off any systemic corticosteroid therapy within 4 weeks of first dose of trial drug.
6. Must be able and willing to discontinue any immunosuppressive agent at screening (e.g. methotrexate, mycophenolate mofetil, 6-mercaptopurine, tacrolimus, cyclophosphamide or azathioprine).
7. No history of severe allergic reactions to monoclonal antibodies.
8. Are able and willing to complete the entire study according to the study schedule.
9. Are willing to forego other forms of experimental treatment during the study.
10. Are able to provide written informed consent.

Exclusion Criteria:

1. History or evidence of a clinically unstable/uncontrolled disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, renal, hepatic, metabolic, hematologic or psychiatric) other than IgG4-RD that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
2. 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).
3. Liver disease: Acute or chronic non-IgG4-related liver disease deemed sufficiently severe to impair their ability to participate in the trial.
4. Uncontrolled disease: evidence of another uncontrolled condition, including drug and alcohol abuse, which could interfere with participation in the trial according to the protocol.
5. Presence of recurrent or chronic infections, defined as ≥3 infections requiring antimicrobials over the past 6 months prior to screening.
6. Active infection requiring hospitalization or treatment with parenteral antimicrobials within the 30 days prior to randomization.
7. Prior use of rituximab (or other B cell depleting agents) within 6 months of enrollment unless B cells have been demonstrated to have repopulated.
8. Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life is unknown) prior to enrollment.
9. White blood cell count < 2.5 x 103/µL.
10. Absolute neutrophil count (ANC) < 1.0 x 103/µL.
11. IgG4-related renal disease with serum creatinine >2.0 mg/dL.
12. Hemoglobin < 10 g/dL.
13. Platelet count < 75 x 109/L.
14. Known positive result for HIV I or II antibody, hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody.
15. Has received live vaccines within 4 weeks of enrollment.
16. Inability to communicate reliably with the investigator.
17. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to end of study (EOS) visit.
18. Positive pregnancy test at screening or during the study.
19. Subjects who do not agree to use medically acceptable methods of contraception.
20. Male patient with a pregnant partner who is not willing to use a condom during the treatment and up to end of study (EOS)visit.
21. Known or suspected sensitivity to mammalian cell-derived products or any components of the study drug.
22. History of alcohol and/or substance abuse within 12 months prior to screening.
23. Unable or unwilling to partake in follow-up assessments or required protocol procedures.

Individual participant data will be shared upon request - without personal health information - following completion of the analysis. Inquiries should be directed to the Principal Investigator.

The primary endpoint is 24 weeks, because this is the duration of time patients were on active treatment. The protocol called for a final study visit at 36 weeks, three months after the patients discontinued their active treatment

Adverse Event monitoring (from time of study drug administration) to end of study (visit 10 (week 36) or safety follow up visit, if needed). Ten subjects were enrolled in the study between December 2018 and August 2019. Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug a nd that does not necessarily have a causal relationship with this treatment.

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity/congenital anomaly. All Serious Adverse Events (SAEs) that occur following the subject's written consent to participate in the study through 30 days of discontinuation of dosing must be reported.

The trial also comes with additional limitations, specifically the small number of patients, the lack of a comparator group, and the open-label design.