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

May 30, 2008 updated by: Rheumazentrum Ruhrgebiet

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)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

149

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Recruiting
        • Erasme University Hospital
        • Contact:
        • Principal Investigator:
          • Serge Steinfeld, Prof.Dr.
      • Diepenbeek, Belgium
        • Recruiting
        • Limburg University Centre
        • Contact:
        • Principal Investigator:
          • Piet Geusens, Prof. Dr.
      • Gent, Belgium, 9000
        • Recruiting
        • Universitair Ziekenhuis, Afdeling Rheumatologie
        • Contact:
        • Principal Investigator:
          • Filip van den Bosch, Dr.
      • Leuven, Belgium, 3000
        • Recruiting
        • University Hospital Leuven
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rene Westhovens, Prof.Dr.
  • Finland
      • Helsinki, Finland, 00029HYKS
        • Recruiting
        • University Central Hospital, Division of Rheumatology
        • Contact:
        • Principal Investigator:
          • Marjatta Leirisalo-Repo, Prof. Dr.
  • France
      • Paris, France
        • Recruiting
        • Groupe Hopitalier Cochin
        • Contact:
        • Principal Investigator:
          • Maxime Breban, Prof.Dr.
      • Paris, France
        • Recruiting
        • Universitat R. Descartes, Hopital Cochin
        • Contact:
        • Contact:
        • Principal Investigator:
          • Maxime Dougados, Prof.Dr.
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charite Mitte
        • Contact:
        • Contact:
        • Principal Investigator:
          • Gerd Burmester, Prof. Dr.
      • Berlin, Germany, 12200
        • Recruiting
        • Charite Klinikum Steglitz
        • Contact:
        • Principal Investigator:
          • Joachim Sieper, Prof.Dr.
      • Herne, Germany, 44652
      • München, Germany, 80336
        • Recruiting
        • Ludwigs-Maximilian-Universität
        • Contact:
        • Principal Investigator:
          • Stefan Schewe, Prof.Dr.
        • Sub-Investigator:
          • Matthias Gruenke, Dr. med.
  • Netherlands
      • Amsterdam, Netherlands, 1007MB
        • Recruiting
        • Academic Ziekenhuis
        • Contact:
        • Contact:
        • Principal Investigator:
          • B.A.C Dijkmans, Prof. Dr.
      • Maastricht, Netherlands, 6202 AZ
        • Recruiting
        • University Hospital Maastricht
        • Contact:
        • Contact:
          • Robert Landewe, Prof. Dr.
          • Phone Number: +31 (0) 43 387 7010
          • Email: Rlan@sint.azm.nl
        • Principal Investigator:
          • Robert Landewe, Prof.Dr.
  • United Kingdom
      • Cambridge, United Kingdom, CB2 QQ
        • Recruiting
        • University of Cambridge/ Clin Med
        • Contact:
        • Principal Investigator:
          • Hill Gaston, Prof.Dr.
      • Leeds, United Kingdom, LS2 9N2
        • Recruiting
        • University of Leeds
        • Contact:
          • Mrs. Keen, Dr.
          • Phone Number: +44 (0) 113 392 24848
        • Contact:
        • Principal Investigator:
          • Paul Emery, Prof.Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
Time Frame: November 2008 and November 2010
November 2008 and November 2010

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients which have received anti-TNF-alpha therapy as standard care after the end of ASSERT
Time Frame: November 2005
November 2005
Description of the various treatment regimens after the end of ASSERT of the participating AS patients in various countries
Time Frame: November 2005
November 2005
Degree of spinal inflammation analyzed by MRI after discontinuation of infliximab and 4-8 weeks and 2 and 4 years after re-treatment
Time Frame: November 2010
November 2010
Long-term efficacy of infliximab over 4 and 6 years of therapy measured by the ASAS response criteria
Time Frame: November 2010
November 2010
Efficacy and safety of a new start of infliximab therapy after discontinuation for several months after 2 and 4 years of continuous treatment
Time Frame: November 2008 and November 2010
November 2008 and November 2010
Long-term effects on QoL
Time Frame: November 2010
November 2010
Long-term effects on health resource utilisation and productivity in paid and unpaid work
Time Frame: November 2010
November 2010

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rheumazentrum Ruhrgebiet

Collaborators

PPD
Centocor BV
Trial Coordination Center, 9713 GZ Groningen

Investigators

  • Principal Investigator: Jürgen Braun, Prof. Dr., Rheumazentrum Ruhrgebiet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Anticipated)

November 1, 2010

Study Completion (Anticipated)

April 1, 2011

Study Registration Dates

First Submitted

October 10, 2005

First Submitted That Met QC Criteria

October 10, 2005

First Posted (Estimate)

October 12, 2005

Study Record Updates

Last Update Posted (Estimate)

June 3, 2008

Last Update Submitted That Met QC Criteria

May 30, 2008

Last Verified

May 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EASIC 30505

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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