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

NCT00432653 | Unknown Phase 2

• 1 other identifier: Ritux-AS-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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

Conditions

Ankylosing Spondylitis

Keywords

ankylosing spondylitis; rituximab; therapy; magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (20)

• Safety Evaluations (Adverse events, vital signs, physical examination results, and clinical laboratory values until week 48)

• Efficacy Evaluations:

• ASAS 40 response

• ASAS criteria for partial remission

• Duration of response

Interventions

rituximab DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Obligatory indication for initiation of established therapy, e.g. with TNFalpha-inhibitors

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Hoffmann-La Roche: collaborator

Study Sites (2)

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

Berlin, 12200, Germany

Location

Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus

Herne, 44652, Germany

Location

Related Publications (8)

• Sieper J, Braun J. Pathogenesis of spondylarthropathies. Persistent bacterial antigen, autoimmunity, or both? Arthritis Rheum. 1995 Nov;38(11):1547-54. doi: 10.1002/art.1780381105.

  PMID: 7488274 BACKGROUND

• Appel H, Loddenkemper C, Grozdanovic Z, Ebhardt H, Dreimann M, Hempfing A, Stein H, Metz-Stavenhagen P, Rudwaleit M, Sieper J. Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther. 2006;8(5):R143. doi: 10.1186/ar2035.

  PMID: 16925803 BACKGROUND

• Appel H, Kuhne M, Spiekermann S, Ebhardt H, Grozdanovic Z, Kohler D, Dreimann M, Hempfing A, Rudwaleit M, Stein H, Metz-Stavenhagen P, Sieper J, Loddenkemper C. Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum. 2006 Sep;54(9):2845-51. doi: 10.1002/art.22060.

  PMID: 16947385 BACKGROUND

• Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC Jr, Dijkmans B, Dougados M, Geher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Bohm H, van Royen BJ, Braun J; 'ASsessment in AS' international working group; European League Against Rheumatism. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2006 Apr;65(4):442-52. doi: 10.1136/ard.2005.041137. Epub 2005 Aug 26.

  PMID: 16126791 BACKGROUND

• Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. doi: 10.1056/NEJMoa032534.

  PMID: 15201414 BACKGROUND

• Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, Racewicz AJ, van Vollenhoven RF, Li NF, Agarwal S, Hessey EW, Shaw TM; DANCER Study Group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006 May;54(5):1390-400. doi: 10.1002/art.21778.

  PMID: 16649186 BACKGROUND

• Sieper J, Baraliakos X, Listing J, Brandt J, Haibel H, Rudwaleit M, Braun J. Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab. Rheumatology (Oxford). 2005 Dec;44(12):1525-30. doi: 10.1093/rheumatology/kei046. Epub 2005 Aug 9.

  PMID: 16091396 BACKGROUND

• Song IH, Heldmann F, Rudwaleit M, Listing J, Appel H, Braun J, Sieper J. Different response to rituximab in tumor necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial. Arthritis Rheum. 2010 May;62(5):1290-7. doi: 10.1002/art.27383.

  PMID: 20461780 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joachim Sieper, MD, Prof.

  Charite, Campus Benjamin-Franklin, Med. Clinic I, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

In-Ho Song, MD

CONTACT

0049-30-8445; in-ho.song@charite.de

Joachim Sieper, MD, Prof.

CONTACT

0049-30-8445; joachim.sieper@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 6, 2007
• First Posted: February 8, 2007
• Study Start: March 1, 2007
• Study Completion: November 1, 2009
• Last Updated: February 8, 2007

Record last verified: 2007-02

Locations

DE (2)