Pilot open label clinical trial with Abatacept in Ankylosing Spondylitis - ABATACEPT-AS-01

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002967-28-DE
• Date of registration: 24/08/2007
• Prospective Registration: Yes
• Primary sponsor: Charité University Medicine
• Public title: Pilot open label clinical trial with Abatacept in Ankylosing Spondylitis - ABATACEPT-AS-01
• Scientific title: Pilot open label clinical trial with Abatacept in Ankylosing Spondylitis - ABATACEPT-AS-01
• Date of first enrolment: 19/10/2007
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002967-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Only patients with moderate to severe ankylosing spondylitis will be included. This implies that only patients with radiological evidence of sacroiliitis (fulfilling the modified New York criteria for AS) will be included.

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 TNFalpha-blocking 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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)
9) nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders
10) Neuropathy that can interfere with quality of life and/or pain assessment.
11) 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.
12) History of current evidence of abuse of “hard” drugs (e.g. cocaine/ heroine) or alcoholism
13) Known hypersensitivity to any component of the study medication
14) Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test)
15) Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier)
16) 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 TNFalapha 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 or rituximab
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. immunoglobulins
9) Receipt of a live vaccine within 4 weeks prior to treatment
10) Intra-articular or par

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

T cell responses have been demonstrated against proteoglycan (an important cartilage protein) in human arthritides including ankylosing spondylitis. We suggest that a chronic, probably T cell mediated, immune response against cartilage is relevant in the pathogenesis of AS. Based on the above described findings about the role of T-cells in ankylosing spondylitis we assume that Abatacept has the potential to be an effective drug for treating ankylosing spondylitis.

Intervention(s)

Trade Name: not applicable
Product Name: Orencia
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Abatacept
CAS Number: 332348-12-6
Current Sponsor code: BMS-188667
Other descriptive name: CTLA4Ig
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Main Objective: The primary endpint will be the ASAS40 response rate in TNF-blocker naïve and in TNF-blocker failure patients at week 24. We postulate that at least 30% of the patients will achieve an ASAS40 response. Given the good efficacy of the TNF-blocking agents, abatacept would not be an interesting treatment if the response rate were lower.

Secondary Objective: Safety Evaluations: Adverse events, vital signs, physical examination results, and clinical laboratory values until week 36.

Efficacy Evaluations: ASAS 20 response, ASAS criteria for partial remission, duration of response, BASDAI 20%, 50%, 70% improvement, BASFI, mobility examinations: BASMI, Chest Wall Expansion, disease controlling antirheumatic therapy criteria (DC-ART20) (5 out of 6), CRP, ESR, quality of Life: SF-36, AS-QoL, EQ-5D; Numeric Rating Scale (NRS) – physicians global, patients global, general pain, nocturnal pain; enthesitis index (Maastricht scale) swollen and tender joint count; socio-economic questionnaire, course of change of active and chronic inflammatory lesions in MRI after 24 weeks Immune monitoring at inclusion and monthly thereafter for 24 weeks: number of T cells, activation of T cells, parameters of apoptosis.

Primary end point(s): The primary endpint will be the ASAS40 response rate in TNF-blocker naïve and in TNF-blocker failure patients at week 24. We postulate that at least 30% of the patients will achieve an ASAS40 response. Given the good efficacy of the TNF-blocking agents, abatacept would not be an interesting treatment if the response rate were lower.

Secondary ID(s)

ABATACEPT-AS-01