Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease

Inclusion Criteria:

1. Diagnosis of CVID according to the international consensus document (ICON)

2. Age 4 years or above

3. Serum IgG at least 2 standard deviations below the age adjusted normal

4. Decreased serum IgA and/or serum IgM

5. Abnormal specific antibody response to immunization

6. Exclusion of secondary immunodeficiency

7. On replacement immunoglobulin for at least 6 months and willing to maintainthroughout study

8. Granulomatous-lymphocytic interstitial lung disease with a lymphocytic componentdiagnosed by lung biopsy prior to study entry, wedge biopsy preferred.

9. Persistence or worsening of interstitial lung disease measured on serial CT imagingof the lung at least 6 months apart, with the latest assessment within 3 months ofstudy entry.

10. Signed written informed consent

11. Willing to allow storage of biological specimens for future use in medical research.

12. Female subjects of childbearing potential must agree to an effective form of birthcontrol such as hormone based contraceptive, intrauterine device, condoms/barrier,surgically sterile partner, or abstinence.

13. Fertile, non-vasectomized males with a female partner of childbearing potentialshould use condoms throughout the study and for 3 months after the last dose

Exclusion Criteria:

1. History of hypersensitivity to abatacept or any of its components

2. Has received any lymphocyte depleting agents including anti-CD20 monoclonalantibodies, alemtuzumab, ATG in the preceding 6 months

3. Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulsesteroids (defined as >15mg/kg/day of methylprednisone or corticosteroid equivalent)within the past 3 months

4. Have started or increased any of the following immune modulating drugs within 3months of enrolling and 3 months from initial CT chest: azathioprine, cyclosporine,tacrolimus, mercaptopurine, methotrexate, mycophenolate mofetil, or sirolimus

5. History of HIV infection (positive PCR)

6. Chronic untreated hepatitis B or C (positive PCR)

7. Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, thenmust supply evidence of completing treatment.

8. Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice atleast 1 month apart

9. Other uncontrolled infections

10. Live vaccine given within 6 weeks of the start of the trial

11. Malignancy or treated for malignancy within the past year

12. Currently pregnant or breast feeding

13. Life expectancy less than 1 month

14. Subjects unwilling to self-administer or have a parent/caregiver self-administersubcutaneous injections at home

15. Other conditions that the investigators feel contraindicate participation in thestudy

Inclusion criteria for Extended Treatment Plan:

• Patients must have completed the abatacept for the treatment of Interstitial LungDisease in Common Variable Immunodeficiency (ABCVILD) trial

• Patients must have demonstrated positive response to abatacept.

• Patients must provide informed consent to participate in the Extended TreatmentPlan.

Exclusion criteria for Extended Treatment Plan:

• Patients who experienced SAEs during the original trial, and such SAEs were determined as related to treatment, or patients who in the opinion of the investigator would not benefit from the extended treatment option.