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Sponsors and Collaborators: |
Charite University, Berlin, Germany Hoffmann-La Roche |
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Information provided by: | Charite University, Berlin, Germany |
ClinicalTrials.gov Identifier: | NCT00432653 |
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
Condition | Intervention | Phase |
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Ankylosing Spondylitis |
Drug: rituximab |
Phase II Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Open Label Clinical Trial With Rituximab (MabThera ®) in Ankylosing Spondylitis |
Estimated Enrollment: | 20 |
Study Start Date: | March 2007 |
Estimated Study Completion Date: | November 2009 |
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 have argued already 10 years ago that autoimmunity plays an important role in the pathogenesis of ankylosing spondylitis (AS). Although there is no direct evidence, as in nearly all ‘suspected’ autoimmune diseases, of an autoimmune response in AS it has been proposed repeatedly over the last years that the cartilage is the most likely target of an autoimmune response in AS. Histological studies 4,5 and magnet resonance imaging investigations suggest that the primary site of inflammation is the cartilage/bone interphase. Mononuclear cell infiltrates are mainly found in cartilage and the subchondral bone. In early and active sacroiliitis, T cells and macrophages are dominant in these infiltrates underlining the relevance of a specific cellular immune response 5.Furthermore, T cell responses have been demonstrated against proteoglycan (an important cartilage protein) in human arthritides including ankylosing spondylitis. We could also recently demonstrate both a CD4+ and a CD8+ T cell response to proteogkycan (aggrecan) derived peptides in the peripheral blood and a CD8+ T cell response against a collagen VI derived peptide in the synovial fluid from AS patients. Thus, all these findings suggest that a chronic, probably T cell mediated, immune response against cartilage is relevant in the pathogenesis of AS.This was further backed by recent studies from our group demonstrating mononuclear infiltrates of cartilage by investigating femoral heads and facette joints (small joints of the spine) obtained by surgery from a number of AS patients). The presence of mononuclear cell infiltrates was strongly dependent on the presence of cartilage on the surface of the femoral heads, suggesting that cartilage could be indeed the stimulus and target of a cellular immune response. However, rather surprisingly there were also dense infiltrations of B cells in the subchondral bone marrow in these patients. In comparison to immunohistological stainings from controls without spinal disease, the number of B cells in AS was even higher than the T cells. At the moment it is not clear whether this indicates that autoantibodies do play a role in the pathogenesis or whether these B cells might rather act as important local antigen presenting cells. In any case, given the assumed autoimmune pathogenesis in AS and the presence of B cells aggregates in inflammatory cellular infiltrates the study of potential effects of an immunotherapy which targets B cells in AS is justified and needed.
Objectives: 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.
Study design: Open label clinical trial with a study duration of 48 weeks
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Exclusion criteria related to general health conditions
Exclusion criteria related to medications
Exclusion criteria related to lab findings
Exclusion criteria related to formal aspects
Contact: In-Ho Song, MD | 0049-30-8445 ext 4895 | in-ho.song@charite.de |
Contact: Joachim Sieper, MD, Prof. | 0049-30-8445 ext 4547 | joachim.sieper@charite.de |
Germany | |
Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus | |
Herne, Germany, 44652 | |
Charite, Campus Benjamin-Franklin, Med. Clinic I, Rheumatology | |
Berlin, Germany, 12200 |
Principal Investigator: | Joachim Sieper, MD, Prof. | Charite, Campus Benjamin-Franklin, Med. Clinic I, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany |
Study ID Numbers: | Ritux-AS-01 |
Study First Received: | February 6, 2007 |
Last Updated: | February 7, 2007 |
ClinicalTrials.gov Identifier: | NCT00432653 |
Health Authority: | Germany: Paul-Ehrlich-Institut |
ankylosing spondylitis rituximab therapy magnetic resonance imaging |
Spinal Diseases Musculoskeletal Diseases Rituximab Spondylarthropathy Arthritis Joint Diseases |
Spondylitis, Ankylosing Spondylarthritis Bone Diseases Spondylitis Ankylosis Spondylarthropathies |
Immunologic Factors Antineoplastic Agents Therapeutic Uses Physiological Effects of Drugs |
Antirheumatic Agents Infection Pharmacologic Actions Bone Diseases, Infectious |