Open label clinical trial with Rituximab (MabThera ®) in Ankylosing Spondylitis - Extension of open label trial: Re-Treatment of patients who have shown response to first course of Rituximab - Ritux-AS-01

• Conditions: 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

• Registration Number: EUCTR2006-002306-64-DE
• Lead Sponsor: Charité Universitaetsmedizin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-04
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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 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 < 8.5 g/dl
25.Neutrophil counts < 1.500 / µl
26.Platelet count < 75.000 / µl
27.Lower than 1 x 1000/µl lymphopenia for more than three months prior to inclusion.
28.Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men.
29.Aspartate

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified