Moderate to severe ankylosing spondylitis who have had an inadequate response to or do not tolerate conventional therapy including NSAIDs, DMARDs and TNF alpha inhibitors
Conditions
Interventions
Trade Name: Rituximab/ Mabthera
Product Name: MabThera
Product Code: Ro45-2294
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
CAS Number: 174722-31
Concentr
Sponsors
Charité Universitaetsmedizin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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 > = 4 plus a back pain score (BASDAI question 2) of >= 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 - 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 - Patients are eligible for a second course of rituximab if they: A) in response assessment period= week 12- week 24: have shown a response after the first administration of rituximab; response defined as reaching ASAS20 criteria (compared to screening) on at least two subsequent time points between week 12 and week 24, B) in flare assessment period (starting from week 24- 48): have a flare after they have shown response (as described above): flare defined as having a 1.5-point-worsening of the BASDAI score in comparison to the lowest BASDAI score between week 12 and week 24, and C) have completed week 24 (re-treatment 24 weeks after first administration of rituximab at the earliest) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria Exclusion criteria related to general health conditions: 1. 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 2. Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms 3. Primary or secondary immunodeficiency 4.History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised 5. 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 6.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. 7.Neuropathy that can interfere with quality of life and/or pain assessment. 8.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. 9.History of current evidence of abuse of “hard” drugs (e.g. cocaine/ heroine) or alcoholism 10.Known hypersensitivity to any component of the product or to murine proteins (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, HCl). 11.Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test) 12.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 13.History of alcohol, drug or chemical abuse within 6 month prior to screening 14.Lack of peripheral venous accessExclusion criteria related to medications 15.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). 16.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 17.Previous treatment with rituximab or intolerance to rituximab 18.Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent within the last 4 weeks prior to the first rituximab infusion 19.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) 20.Previous treatment with any investigational agent 21.Previous treatment with i.v. immunoglobulins 22.Receipt of a live vaccine within 4 weeks prior to treatment 23.Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visitExclusion criteria related to lab findings 24.Haemoglobin 1.4 mg/dl for women or 1.6 mg/dl for men. 29.Aspartate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. Primary endpoint: Efficacy Evaluation in week 24 and until study end: ASAS 20 in AS patients naïve to TNFalpha inhibitors as well as in AS patients with previous therapy with TNFalpha inhibitors. Patients who have shown good response to initial treatment with Rituximab (good response defined as reaching ASAS20 criteria on two consecutive visitis between week 12 and week 24) are eligible for a second course of Rituximab if they show a flare of their disease (flare defined as a 1.5-point-worsening of the BASDAI score between week 24 and 48 compared to the best BASDAI score between week 12 and 24). Primary endpoint for patients who are re-treated: ASAS20 response at week R-24. ;Secondary Objective: Secondary endpoints: Safety Evaluations: Adverse events, vital signs, physical examination results, and clinical laboratory values until week (R-) 48. Efficacy Evaluations: ASAS 40 response, ASAS criteria for partial remission, 20%, 50% and 70% improvement of disease activity (BASDAI), improvement of BASMI, BASFI, SF-36, number of swollen joints, number of enthesitic regions (Maastricht Index), regression of inflammation (CRP, ESR), patients– and physicians global assessment, general and nocturnal pain, EQ-5D, socioeconomic questionnaire, MRI for acute and chronic lesions at 24 weeks and at 48 weeks compared to screening for patients receiving course 1 and MRI for acute and chronic lesions at week R-24 and R-48 for patients receiving course 2 (re-treatment), B cell and T cell analysis at weeks (R-) 4, (R-) 12, (R-) 24 and (R-) 48 for patients receiving course 1 (or(and) 2. ;Primary end point(s): Primary endpoint: Efficacy Evaluation in week 24 and until study end: ASAS 20 in AS patients naïve to TNFalpha inhibitors as well as in AS patient | — |
Countries
Germany
Outcome results
None listed