Examination of Radiographic Progression, Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis

Ankylosing Spondylitis Clinical Trial

Official title:

An Open Label Extension, Investigator Initiated Trial to Examine Radiographic Progression , Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis. EASIC (European Ankylosing Spondylitis Infliximab Cohort)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00237419
• Other study ID #: EASIC 30505
• Status: Recruiting
• Phase: N/A
• First received: October 10, 2005
• Last updated: May 30, 2008
• Start date: December 2005
• Est. completion date: April 2011

Study information

• Verified date: May 2008
• Source: Rheumazentrum Ruhrgebiet
• Contact: Jürgen Braun, Prof. Dr.
• Phone: +49 (0) 2325 592131
• Email: j.braun[@]rheumazentrum-ruhrgebiet.de
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

Ankylosing spondylitis (AS) is a chronic inflammatory disease that involves the sacroiliac joints, axial skeleton, entheses and peripheral joints. Current therapy for AS is mainly NSAIDs and physiotherapy which are oft insufficient. Treatment with the TNF-alpha blocking agent infliximab was shown to have definite clinical efficacy in patients with active AS on a short- and a long-term-basis over 2 years. We want to show that treatment with infliximab on a long-term basis over 4 years is safe and efficient and can prevent radiographic progression over a long period of time. Further we want to learn about the outcome after discontinuation of anti-TNF-alpha therapy.

Description:

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology that involves the sacroiliac joints, axial skeleton, entheses and peripheral joints. Chronic inflammation of entheses leads to new bone formation, syndesmophytes and ankylosis of joints, primarily in the axial skeleton. This leads to a dramatic loss of range of motion and to disability. The disease may also have nonskeletal manifestations including uveitis, carditis, pulmonary fibrosis and cardiac conduction abnormalities.

Current therapy for AS is mainly with NSAIDs and physiotherapy which are often insufficient. Clinical outcome with conventional therapies has not been good, with 50-70% of patients progressing to fusion of the spine by 10 to 15 years. Treatment with the TNF-alpha blocking agent infliximab was shown to have definite clinical efficacy in patients with active ankylosing spondylitis on a short- and a long-term basis over 2 years.

There is limited data available on the efficacy and safety of long-term anti-TNF therapy for 3 and more years, the outcome after discontinuation of anti-TNF therapy and the effect of anti-TNF therapy on radiographic progression over a long period of time.

The ASSERT trial was a 2 year international randomized placebo controlled trial to evaluate the efficacy and safety ot treatment with infliximab in patients with active and severe AS. The EASIC trial is initiated to follow the European participants of the ASSERT trial for at least an additional 2 years of treatment combined with systematic data collection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 149
• Est. completion date: April 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients in Europe who have completed visit "week 96" of ASSERT (last infusion of infliximab)

• Capacity to understand and sign an informed consent form

• Capacity to read and understand subject assessment forms

• Using adequate birth control measures for the duration of the study and for 6 months after receiving the last infusion, if the patient is of childbearing potential

• Serum creatinine < 1,4 mg/dl

• Hemoglobin > 9,0 mg /dl for males and > 8,5 mg/dl for females

• Serum transaminase levels within 3 times the upper limit of normal range

Exclusion Criteria:

• Have used systemic prednisolone > 20 mg during the 2 weeks prior to screening

• Have used cytotoxic drugs after the end of ASSERT including chlorambucil, cyclophosphamide and alkylating agents

• Have received any previous treatment with etanercept or any other anti-TNF agent (other than infliximab) after the end of the ASSERT trial

• General medical exclusion criteria

• Use of any investigational drug within 30 days prio to screening

• Concomitant diagnosis or history of congestive heart failure

• History of latent or active tuberculosis

• Signs or symptoms suggestive of active tuberculosis

• Recent close contact with a person with active tuberculosis

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• infliximab
Infliximab infusions 5 mg/kg body-weight each 6 to 8 weeks

Locations

Country	Name	City	State
Belgium	Erasme University Hospital	Brussels
Belgium	Limburg University Centre	Diepenbeek
Belgium	Universitair Ziekenhuis, Afdeling Rheumatologie	Gent
Belgium	University Hospital Leuven	Leuven
Finland	University Central Hospital, Division of Rheumatology	Helsinki
France	Groupe Hopitalier Cochin	Paris
France	Universitat R. Descartes, Hopital Cochin	Paris
Germany	Charite Klinikum Steglitz	Berlin
Germany	Charite Mitte	Berlin
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Ludwigs-Maximilian-Universität	München
Netherlands	Academic Ziekenhuis	Amsterdam
Netherlands	University Hospital Maastricht	Maastricht
United Kingdom	University of Cambridge/ Clin Med	Cambridge
United Kingdom	University of Leeds	Leeds

Sponsors (4)

Lead Sponsor	Collaborator
Rheumazentrum Ruhrgebiet	Centocor BV, PPD, Trial Coordination Center, 9713 GZ Groningen

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Degree of structural damage (radiographic progression)after 4 and 6 years of infliximab therapy (2 years of ASSERT trial plus 2 years of EASIC trial)		November 2008 and November 2010	No
Secondary	Proportion of patients which have received anti-TNF-alpha therapy as standard care after the end of ASSERT		November 2005	No
Secondary	Description of the various treatment regimens after the end of ASSERT of the participating AS patients in various countries		November 2005	No
Secondary	Degree of spinal inflammation analyzed by MRI after discontinuation of infliximab and 4-8 weeks and 2 and 4 years after re-treatment		November 2010	No
Secondary	Long-term efficacy of infliximab over 4 and 6 years of therapy measured by the ASAS response criteria		November 2010	No
Secondary	Efficacy and safety of a new start of infliximab therapy after discontinuation for several months after 2 and 4 years of continuous treatment		November 2008 and November 2010	Yes
Secondary	Long-term effects on QoL		November 2010	No
Secondary	Long-term effects on health resource utilisation and productivity in paid and unpaid work		November 2010	No