Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00432653
Status:
UNKNOWN
Last Update Posted:
2007-02-08
First Post:
2007-02-06
Brief Title:
Open Label Clinical Trial With Rituximab MabThera in Ankylosing Spondylitis
Sponsor:
Charite University Berlin Germany
Organization:
Charite University Berlin Germany
Study Overview
Official Title:
Open Label Clinical Trial With Rituximab MabThera in Ankylosing Spondylitis
Status:
UNKNOWN
Status Verified Date:
2007-02
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 spondylitis
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 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 45 and magnet resonance imaging investigations suggest that the primary site of inflammation is the cartilagebone 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 5Furthermore 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 ASThis 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
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 45 and magnet resonance imaging investigations suggest that the primary site of inflammation is the cartilagebone 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 5Furthermore 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 ASThis 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None