Pilot Open Label Clinical Trial With Abatacept in Ankylosing Spondylitis

• Status: Unknown status
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charite University, Berlin, Germany
• Collaborator: Bristol-Myers Squibb
• Treatments: Abatacept

Criteria

Inclusion Criteria:

Patients 18 - 65 years of age who have moderate to severe ankylosing spondylitis.

1. Patients 18- 65 years of age who have moderate to severe ankylosing spondylitis.

2. Group

1. 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

2. 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)

3. 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)

4. 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.

5. 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

6. If on sulfasalazine or methotrexate, must be stable for 4 weeks prior to baseline

7. 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.

Exclusion Criteria:

Main Inclusion/Exclusion Criteria

Exclusion criteria related to general health conditions

1. 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

2. 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 (other manifestations of spondyloarthritis such as psoriasis, inflammatory bowel disease, arthritis, uveitis are not regarded as exclusion criteria)

3. Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms

4. Hepatitis B or C or HIV

5. Primary or secondary immunodeficiency

6. History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised

7. 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

8. 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.

9. Neuropathy that can interfere with quality of life and/or pain assessment.

10. 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.

11. History of current evidence of abuse of "hard" drugs (e.g. cocaine/ heroine) or alcoholism

12. Known hypersensitivity to any component of the study medication

13. Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test)

14. Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier)

15. History of alcohol, drug or chemical abuse within 6 month prior to screening

Exclusion criteria related to medications

1. if previously on TNFalpha blocking agents, discontinuation of TNFalpha-blocking agents because of intolerance

2. If on leflunomide, leflunomide must have been terminated at least 8 weeks prior to the first abatacept administration (or ≥ 28 days after 11 days of standard cholestyramine or activated charcoal washout).

3. If on TNFalpha blocking agent (infliximab, etancercept, adalimumab), the TNFa therapy must have been terminated at least 4 weeks prior to the first abatacept adminstration if etanercept was used and at least 8 weeks if infliximab or adalimumab were used

4. Previous treatment with abatacept

5. If on sulfasalazine or methotrexate, must be stable for 4 weeks prior to baseline

6. Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent within the last 4 weeks prior to the first abatacept administration

7. Previous treatment with any investigational agent within 28 days ( or less than 5 terminal half-lives of elimination) of day 1 dose

8. Previous treatment with i.v. immunoglobulin

9. Receipt of a live vaccine within 4 weeks prior to treatment

10. Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit

Exclusion criteria related to lab findings

1. Haemoglobin < 8.5 g/dl

2. Neutrophil counts < 2.000 / µl

3. Platelet count < 125.000 / µl

4. Lower than 1 x 1000/µl lymphopenia for more than three months prior to inclusion.

5. Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men.

6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal

7. Positive HIV, hepatitis B or C serology

8. Any other laboratory test result that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.

Exclusion criteria related to formal aspects

1. Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days.

2. 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).