Safety and Efficacy of Abatacept in IgG4-Related Disease
Condition: IgG4-related Disease
MeSH terms: Immunoglobulin G4-Related Disease
Intervention: Abatacept
Intervention description: Subjects will receive weekly subcutaneous doses of abatacept (125mg) for 24 doses (24 weeks)
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.