Pilot Open Label Clinical Trial With Abatacept in Ankylosing Spondylitis

NCT00558506 | Unknown Phase 2

• 1 other identifier: ABATACEPT-AS-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label trial investigating the efficacy and safety of abatacept in ankylosing spondylitis. It is planned to treat 30 patients with ankylosing spondylitis from baseline up to week 30. Abatacept will be administered intravenously according to the prescription used in rheumatoid arthritis.

Conditions

Ankylosing Spondylitis

Keywords

Ankylosing spondylitis; activity; treatment; clinical trial

Outcome Measures

Primary Outcomes (1)

• ASAS40 response rate in TNF-blocker naïve and in TNF-blocker failure patients

  at week 24

Secondary Outcomes (15)

• Safety Evaluations: Adverse events, vital signs, physical examination results, and clinical laboratory values

  until week 36

• ASAS20 response

  througout study

• ASAS partial remission criteria

  throughout study

• BASDAI 20 response

  throughout study

• BASDAI 50 response

  throughout study

Study Arms (1)

A

EXPERIMENTAL

Abatacept

Drug: abatacept

Interventions

abatacept DRUG

intravenously 750mg (in patients with weight of 60- 100kg)

A

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.
• Patients 18- 65 years of age who have moderate to severe ankylosing spondylitis.
• Group
• TNFalpha inhibitor naïve patients: active AS patients with inadequate response to conventional therapy (e.g. NSAIDs, glucocorticosteroids or DMARDs) or with intolerance of conventional therapy Group
• TNFalpha inhibitor failures: active AS patients with inadaequate response to treatment with TNFalpha inhibitors (= patients with previous treatment with TNFalpha inhibitors who showed an inadaquate response according to the international ASAS recommendations; NOT AS patients who had to discontinue TNFalpha inhibitor treatment because of intolerance)
• active disease is defined as a BASDAI score of\>= 4, back pain score (BASDAI question 2) of \>= 4 despite concurrent NSAID therapy, or intolerance to NSAIDs (first group) or prior treatment with TNFalpha inhibitors (second group)
• if on NSAIDs, dosage must be stable 2 weeks prior to baseline. During the study dosage should be stable but is allowed to be reduced if documentated.
• If on prednisone, \<=10.0 mg per day, must be stable for 4 weeks prior to baseline and should be kept stable during the study
• If on sulfasalazine or methotrexate, must be stable for 4 weeks prior to baseline
• If on TNFalpha blocking agent (infliximab, etancercept, adalimumab), the TNFa therapy must have been terminated at least 4 weeks prior to baseline if etanercept was used and at least 8 weeks if infliximab or adalimumab were used.

You may not qualify if:

• Current clinical or laboratory evidence of active or latent tuberculosis (TB) and subjects with a history of active TB treated within the last 3 years --\> all potential subjects will have a screening chest x-ray at baseline (acceptable if present within the last 3 months); all potential subjects will have a Tuberculin skin test at screening
• Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms
• Hepatitis B or C or HIV
• 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 study medication
• 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)
• History of alcohol, drug or chemical abuse within 6 month prior to screening
• if previously on TNFalpha blocking agents, discontinuation of TNFalpha-blocking agents because of intolerance

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Charité University Medicine Berlin, Campus Benjamin-Franklin

Berlin, 12200, Germany

RECRUITING

Rheumazentrum Ruhrgebiet

Herne, 44652, Germany

RECRUITING

Related Publications (8)

• 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

• 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

• 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, Kohler D, Zacher J, Stein H, Sieper J, Loddenkemper C. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum. 2006 Jun;54(6):1805-13. doi: 10.1002/art.21907.

  PMID: 16736521 BACKGROUND

• 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

• Maksymowych WP. Ankylosing spondylitis--at the interface of bone and cartilage. J Rheumatol. 2000 Oct;27(10):2295-301. No abstract available.

  PMID: 11036819 BACKGROUND

• Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study. Arthritis Rheum. 2006 Sep;54(9):2807-16. doi: 10.1002/art.22070.

  PMID: 16947384 BACKGROUND

• Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006 Jun 20;144(12):865-76. doi: 10.7326/0003-4819-144-12-200606200-00003.

  PMID: 16785475 BACKGROUND

MeSH Terms

Conditions

Spondylitis, Ankylosing; Motor Activity

Interventions

Abatacept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Joachim Sieper, MD

  Charité University Medicine Berlin, Campus Benjamin Franklin, Medical Department I, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joachim Sieper, MD

CONTACT

+49-(0)30-8445-; joachim.sieper@charite.de

In-Ho Song, MD

CONTACT

+49-(0)30-8445-; in-ho.song@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: November 14, 2007
• First Posted: November 15, 2007
• Study Start: January 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 26, 2008

Record last verified: 2007-09

Locations

DE (2)