Clinical trial NCT00432653 (phase 2/phase 3, status: unknown status)
Conditions: ankylosing spondylitis
ICD codes: M08.1, M45.6, M45.2, M45.3, M45.4, M45.5, M45.7
Drugs: rituximab
SMILES: ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        Inclusion Criteria:

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

          -  Active disease is defined as a BASDAI score of ³ 4 plus a

          -  back pain score (BASDAI question 2) of ³ 4 despite concurrent NSAID therapy, or
             intolerance to NSAIDs

          -  If on prednisone, £10 mg per day must be stable for 4 weeks prior to baseline.

          -  If on methotrexate, £ 25 mg per week must be stable for 4 weeks prior to baseline

          -  If on sulfasalazine, must be stable 4 weeks prior to basline

          -  Women of child bearing potential must have a negative pregnancy urine test at study
             baseline and use an adequate, effective method of contraception (such as implants,
             injectables, combined oral contraceptives, some IUDs, sexual abstinence, vasectomised
             partner) for a duration of 12 months after stop of rituximab therapy.

          -  Sexual active men must use an accepted method of contraception for a duration of 12
             months after first administration of rituximab.

          -  Willingness and capability to give written informed consent, written consent for data
             protection (legal requirement in Germany: datenschutzrechtliche Einwilligung) and
             willingness to participate and to comply with the study

        Exclusion Criteria:

        Exclusion criteria related to general health conditions

          -  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

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

          -  Primary or secondary immunodeficiency

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

          -  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

          -  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.

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

          -  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.

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

          -  Known hypersensitivity to any component of the product or to murine proteins (sodium
             citrate, polysorbate 80, sodium chloride, sodium hydroxide, HCl).

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

          -  Males or females of reproductive potential not willing to use effective contraception
             (e.g. contraceptive pill, IUD, physical barrier) for up to 12.5 months after first
             infusion of rituximab

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

          -  Lack of peripheral venous access

        Exclusion criteria related to medications

          -  Obligatory indication for initiation of established therapy, e.g. with
             TNFalpha-inhibitors

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

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

          -  Previous treatment with rituximab or intolerance to rituximab

          -  Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent
             within the last 4 weeks prior to the first rituximab infusion

          -  Intolerance or contraindication to drugs required for the treatment of the side
             effects of rituximab (e.g. paracetamol, acetaminophen, diphenhydramine, p.o. and i.v.
             corticosteroids, anti-emetics or H1 blockers

          -  Previous treatment with any investigational agent

          -  Previous treatment with i.v. immunoglobulins

          -  Receipt of a live vaccine within 4 weeks prior to treatment

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

        Exclusion criteria related to lab findings

          -  Haemoglobin < 8.5 g/dl

          -  Neutrophil counts < 2.000 / µl

          -  Platelet count < 125.000 / µl

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

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

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

          -  Positive HIV, hepatitis B or C serology

        Exclusion criteria related to formal aspects

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

          -  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).

          -  Patients who are institutionalised due to regulatory or juridical order (according to
             AMG § 40 (1) Abs. 4)