Status:

UNKNOWN

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

Lead Sponsor:

Charite University, Berlin, Germany

Collaborating Sponsors:

Hoffmann-La Roche

Conditions:

Ankylosing Spondylitis

Eligibility:

All Genders

18-65 years

Phase:

PHASE2

PHASE3

Brief 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 s...

Detailed Description

Indication: 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. Rationale: We h...

Eligibility Criteria

Inclusion

  • 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

  • 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)

Key Trial Info

Start Date :

March 1 2007

Trial Type :

INTERVENTIONAL

End Date :

November 1 2009

Estimated Enrollment :

20 Patients enrolled

Trial Details

Trial ID

NCT00432653

Start Date

March 1 2007

End Date

November 1 2009

Last Update

February 8 2007

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Charite, Campus Benjamin-Franklin, Med. Clinic I, Rheumatology

Berlin, Germany, 12200

2

Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus

Herne, Germany, 44652