Pilot Open Label Clinical Trial With Abatacept in Ankylosing Spondylitis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00558506
• Date of registration: 14/11/2007
• Prospective Registration: Yes
• Primary sponsor: Charite University, Berlin, Germany
• Public title: Pilot Open Label Clinical Trial With Abatacept in Ankylosing Spondylitis Aba-AS-01
• Scientific title: Pilot Open Label Clinical Trial With Abatacept in Ankylosing Spondylitis
• Date of first enrolment: January 2008
• Target sample size: 30
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT00558506
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Germany

Contacts

• Name: Joachim Sieper, MD

• Name: Joachim Sieper, MD
• Affiliation: Charité University Medicine Berlin, Campus Benjamin Franklin, Medical Department I, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis

Intervention(s)

Drug: abatacept

Primary Outcome(s)

ASAS40 response rate in TNF-blocker naïve and in TNF-blocker failure patients [Time Frame: at week 24]

Secondary Outcome(s)

Socio-economic questionnaire [Time Frame: throughout the study]

BASDAI 50 response [Time Frame: throughout study]

course of change of active and chronic inflammatory lesions in MRI [Time Frame: throughout the study]

erythrocyte sedimentation rate [Time Frame: throughout study]

Quality of Life: SF-36, AS-QoL, EQ-5D [Time Frame: Quality of Life: SF-36, AS-QoL, EQ-5D]

BASMI [Time Frame: throughout study]

C-reactive protein [Time Frame: throughout study]

Numeric Rating Scale (NRS) - physicians global, patients global, general pain, nocturnal pain [Time Frame: throughout the study]

swollen and tender joint count [Time Frame: swollen and tender joint count]

BASFI [Time Frame: throughout study]

ASAS partial remission criteria [Time Frame: throughout study]

ASAS20 response [Time Frame: througout study]

Enthesitis index (Maastricht scale) [Time Frame: throughout the study]

Safety Evaluations: Adverse events, vital signs, physical examination results, and clinical laboratory values [Time Frame: until week 36]

BASDAI 20 response [Time Frame: throughout study]

Secondary ID(s)

ABATACEPT-AS-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bristol-Myers Squibb