Open Label Clinical Trial With Rituximab (MabThera ®) in Ankylosing Spondylitis

• Status: Unknown status
• Trial end date: 2009-11-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the efficacy and safety of rituximab when added to NSAIDs and/ or methotrexate both for TNFalpha inhibitor naïve or TNFalpha inhibitor failure patients with moderate to severe ankylosing spondylitis

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charite University, Berlin, Germany
• Collaborator: Hoffmann-La Roche
• Treatments: Rituximab

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)