Safety and Efficacy of Abatacept in IgG4-Related Disease

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.