Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Abatacept; Placebo
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This is a randomized, double blind, placebo controlled trial of abatacept for the treatment
      of lupus arthritis and other manifestations of lupus. Patients with lupus and at least 3
      tender and 3 swollen joints and </= 20 mg prednisone have other background immune
      suppressants withdrawn at entry. They can elect to receive up to a total of 320 mg depomedrol
      (in two or more injections) between the screening visit and the visit 2 months after dosing
      begins. Abatacept (125 mg) or placebo is administered in weekly subcutaneous doses. After 3
      months of treatment patients who are not responding may elect to receive open label abatacept
      with or without additional standard of care therapies. Such patients are considered non
      responders. The primary endpoint is the British Isles Lupus Assessment Group Index
      (BILAG)-linked Combined Lupus Assessment (BICLA) which will require a clinically significant
      improvement in arthritis and other active features of lupus
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Written Informed Consent

          2. Four 1997 revised ACR Classification Criteria for SLE

          3. Active polyarticular arthritis meeting at minimum BILAG 2004 B definition with a
             minimum of 3 tender and 3 swollen joints observed at the screening visit

          4. Men and women 18 to 70 years of age.

          5. Women of childbearing potential and men with partners of childbearing potential must
             use an acceptable method of birth control throughout the study

          6. Women of childbearing potential must have a negative urine pregnancy test at screening
             and Study Day 1 (baseline visit) and may not be breast feeding

        Exclusion Criteria:

          1. Current severe, organ-threatening disease (e.g. acute nephritis appropriate for
             induction therapy, CNS lupus (excepting chorea, cranial neuropathy, and resolving
             optic neuritis) or any lupus condition requiring cyclophosphamide, biologic therapy,
             or IV bolus steroids of >/= 500 mg.

          2. Subjects who are incapable of understanding or completing study-related assessments.

          3. Subjects with any condition, whether or not related to SLE, which, in the opinion of
             the investigator, might place a subject at unacceptable risk for participation in the
             study.

          4. Subjects with a history of cancer in the last 5 years, other than non-melanoma skin
             cell cancers cured by local resection or carcinoma in situ.

          5. Subjects who currently abuse drugs or alcohol.

          6. Subjects with acute herpes zoster or cytomegalovirus (CMV) within 2 months of
             screening.

          7. Subjects who have received any live vaccines within 3 months of first dose.

          8. Subjects with any serious bacterial infection within the last 3 months, unless treated
             and resolved with antibiotics, or any chronic bacterial infection (eg, chronic
             pyelonephritis, osteomyelitis, or bronchiectasis).

          9. Subjects at risk for tuberculosis (TB).

         10. Subjects known to be positive for hepatitis B surface antigen or hepatitis C unless
             negative by PCR or RIBA

         11. Acute hemolytic anemia with hemoglobin < 7.0 g/dL or known change in Hg by 2.0 g/dL
             within four months

         12. WBC < 2500/mm3 (< 3 x 109/L) unless due to chronic stable lupus activity

         13. Platelets < 40,000/mm3 (< 3 x 109/L) (If less than 100,000 must have been stable
             (within a range of 10,000/mm3 ) within two months of screening or in two tests during
             the screening period.

         14. Serum creatinine > 2 times the ULN

         15. Serum ALT or AST > 2.5 times the ULN

         16. Any other laboratory test results that, in the opinion of the investigator, might
             place a subject at unacceptable risk for participation in the study.

         17. Known allergy/sensitivity to the study agent or carrier.

         18. Treatment with investigational drug within 28 days (or 5 terminal half-lives) of the
             Day 1 dose.

         19. Cyclophosphamide within 3 months of Day 1 or bolus IV steroids >/=500 mg within 1
             month

         20. Prednisone > 20 mg qd after the screening visit

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