Clinical trial NCT00558506 (phase 2, status: unknown status)
Conditions: ankylosing spondylitis
ICD codes: M08.1, M45.6, M45.2, M45.3, M45.4, M45.5, M45.7
Drugs: abatacept
SMILES: [H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O
Eligibility criteria:

        Inclusion Criteria:

        Patients 18 - 65 years of age who have moderate to severe ankylosing spondylitis.

          1. Patients 18- 65 years of age who have moderate to severe ankylosing spondylitis.

          2. Group

               1. TNFalpha inhibitor naïve patients: active AS patients with inadequate response to
                  conventional therapy (e.g. NSAIDs, glucocorticosteroids or DMARDs) or with
                  intolerance of conventional therapy Group

               2. TNFalpha inhibitor failures: active AS patients with inadaequate response to
                  treatment with TNFalpha inhibitors (= patients with previous treatment with
                  TNFalpha inhibitors who showed an inadaquate response according to the
                  international ASAS recommendations; NOT AS patients who had to discontinue
                  TNFalpha inhibitor treatment because of intolerance)

          3. active disease is defined as a BASDAI score of>= 4, back pain score (BASDAI question
             2) of >= 4 despite concurrent NSAID therapy, or intolerance to NSAIDs (first group) or
             prior treatment with TNFalpha inhibitors (second group)

          4. if on NSAIDs, dosage must be stable 2 weeks prior to baseline. During the study dosage
             should be stable but is allowed to be reduced if documentated.

          5. If on prednisone, <=10.0 mg per day, must be stable for 4 weeks prior to baseline and
             should be kept stable during the study

          6. If on sulfasalazine or methotrexate, must be stable for 4 weeks prior to baseline

          7. If on TNFalpha blocking agent (infliximab, etancercept, adalimumab), the TNFa therapy
             must have been terminated at least 4 weeks prior to baseline if etanercept was used
             and at least 8 weeks if infliximab or adalimumab were used.

        Exclusion Criteria:

        Main Inclusion/Exclusion Criteria

        Exclusion criteria related to general health conditions

          1. Current clinical or laboratory evidence of active or latent tuberculosis (TB) and
             subjects with a history of active TB treated within the last 3 years --> all potential
             subjects will have a screening chest x-ray at baseline (acceptable if present within
             the last 3 months); all potential subjects will have a Tuberculin skin test at
             screening

          2. Patients with other chronic inflammatory articular disease or systemic autoimmune
             disease, e.g. Systemic lupus erythematosus, Sjögren's syndrome, active rheumatoid
             vasculitis, a history of systemic diseases associated with arthritis, chronic fatigue
             syndrome (other manifestations of spondyloarthritis such as psoriasis, inflammatory
             bowel disease, arthritis, uveitis are not regarded as exclusion criteria)

          3. Any active infection, a history of recurrent clinically significant infection, a
             history of recurrent bacterial infections with encapsulated organisms

          4. Hepatitis B or C or HIV

          5. Primary or secondary immunodeficiency

          6. History of cancer with curative treatment not longer than 5 years ago except
             basal-cell carcinoma of the skin that had been excised

          7. A history of pulmonary or cardiac insufficiency, or serious and/or uncontrolled
             diseases that are likely to interfere with the evaluation of the patient's safety and
             of the study outcome

          8. Evidence of significant uncontrolled concomitant diseases such as cardiovascular
             disease ( e.g. heart failure class III/IV NYHA, cardiac infarct within last 6 month),
             nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.

          9. Neuropathy that can interfere with quality of life and/or pain assessment.

         10. Patients with a history of a severe psychological illness or condition such as to
             interfere with the patient's ability to understand the requirements of the study.

         11. History of current evidence of abuse of "hard" drugs (e.g. cocaine/ heroine) or
             alcoholism

         12. Known hypersensitivity to any component of the study medication

         13. Women lactating, pregnant, nursing or of childbearing potential with a positive
             pregnancy test (urine test)

         14. Males or females of reproductive potential not willing to use effective contraception
             (e.g. contraceptive pill, IUD, physical barrier)

         15. History of alcohol, drug or chemical abuse within 6 month prior to screening

        Exclusion criteria related to medications

          1. if previously on TNFalpha blocking agents, discontinuation of TNFalpha-blocking agents
             because of intolerance

          2. If on leflunomide, leflunomide must have been terminated at least 8 weeks prior to the
             first abatacept administration (or ≥ 28 days after 11 days of standard cholestyramine
             or activated charcoal washout).

          3. If on TNFalpha blocking agent (infliximab, etancercept, adalimumab), the TNFa therapy
             must have been terminated at least 4 weeks prior to the first abatacept adminstration
             if etanercept was used and at least 8 weeks if infliximab or adalimumab were used

          4. Previous treatment with abatacept

          5. If on sulfasalazine or methotrexate, must be stable for 4 weeks prior to baseline

          6. Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent
             within the last 4 weeks prior to the first abatacept administration

          7. Previous treatment with any investigational agent within 28 days ( or less than 5
             terminal half-lives of elimination) of day 1 dose

          8. Previous treatment with i.v. immunoglobulin

          9. Receipt of a live vaccine within 4 weeks prior to treatment

         10. Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit

        Exclusion criteria related to lab findings

          1. Haemoglobin < 8.5 g/dl

          2. Neutrophil counts < 2.000 / µl

          3. Platelet count < 125.000 / µl

          4. Lower than 1 x 1000/µl lymphopenia for more than three months prior to inclusion.

          5. Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men.

          6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper
             limit of normal

          7. Positive HIV, hepatitis B or C serology

          8. Any other laboratory test result that, in the opinion of the investigator, might place
             the subject at unacceptable risk for participation in this study.

        Exclusion criteria related to formal aspects

          1. Patients who participate currently in another clinical trial or patients who
             participated in another clinical trial during the last 30 days.

          2. Patients who are underage or patients who are incapable to understand the aim,
             importance and consequences of the study and to give legal informed consent (according
             to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG).