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Ustekinumab for the Treatment of Patients With Active Ankylosing Spondylitis (TOPAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01330901
Recruitment Status : Completed
First Posted : April 7, 2011
Last Update Posted : June 4, 2013
Sponsor:
Information provided by (Responsible Party):
J. Sieper, Charite University, Berlin, Germany

Tracking Information
First Submitted Date  ICMJE April 5, 2011
First Posted Date  ICMJE April 7, 2011
Last Update Posted Date June 4, 2013
Study Start Date  ICMJE October 2011
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2011)
The Assessment of Spondyloarthritis International Society (ASAS)40 response [ Time Frame: week 24 ]
The percentage of patients who achieved ASAS40 response defined as an improvement of ≥40% and ≥2 points in at least 3 out of four following domains (and no worsening in remaining domain):
  • Patient global
  • Pain
  • Function (as measured by the Bath Ankylosing Spondylitis Functional Index - BASFI)
  • Inflammation (mean of the Bath Ankylosing Spondylitis Disease Activity Index - BASDAI question 5 and 6)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2011)
  • The Assessment of Spondyloarthritis International Society (ASAS)20 response at week 24 [ Time Frame: Week 24 ]
    The percentage of patients who achieved ASAS20 response defined as an improvement of ≥20% and ≥1 points in at least 3 out of four following domains (and no worsening of ≥20% and ≥1 points in remaining domain):
    • Patient global
    • Pain
    • Function (as measured by the Bath Ankylosing Spondylitis Functional Index - BASFI)
    • Inflammation (mean of the Bath Ankylosing Spondylitis Disease Activity Index - BASDAI question 5 and 6)
  • The Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement [ Time Frame: Week 24 ]
    The percentage of patients who achieved the ASDAS clinically important improvement (≥1.1) at week 24
  • The Assessment of Spondyloarthritis International Society (ASAS) partial remission [ Time Frame: Week 24 ]
    The percentage of patients who achieved partial remission according to the ASAS definition at week 24
  • The Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement [ Time Frame: Week 24 ]
    The percentage of patients who achieved the ASDAS major improvement (≥2.0) at week 24
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Week 28 ]
    Number of participants with adverse events as a measure of safety and tolerability up to week 28
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ustekinumab for the Treatment of Patients With Active Ankylosing Spondylitis
Official Title  ICMJE UsTekinumab for the Treatment Of Patients With Active Ankylosing Spondylitis (TOPAS) - a 28-week, Prospective, Open-label, Proof-of-concept Study
Brief Summary This study is aimed at investigation of efficacy and safety of ustekinumab (monoclonal antibody against interleukin 12 and 23) treatment in patients with active ankylosing spondylitis (AS) fulfilling the modified New York criteria who have had an inadequate response to standard therapy with non-steroidal anti-inflammatory drugs (NSAIDs) or do not tolerate or have a contraindication for NSAIDs.
Detailed Description This study is a prospective, open-label, proof-of-concept clinical trial that will be conducted in a referral center for patients with AS in Berlin. Eligible patients will be treated with ustekinumab 90 mg given subcutaneously at weeks 0, 4, and 16. The entire study period accounts 28 weeks. Assessment of the primary outcome parameter will be performed at week 24. The patients will be closely monitored throughout the study on a total of 9 visits.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ankylosing Spondylitis
Intervention  ICMJE Drug: Ustekinumab
Ustekinumab 90 mg given subcutaneously at weeks 0, 4, and 16
Other Name: Stelara
Study Arms  ICMJE Experimental: Ustekinumab
Ustekinumab 90 mg subcutaneously at week 0, 4 and 16
Intervention: Drug: Ustekinumab
Publications * Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J. Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014 May;73(5):817-23. doi: 10.1136/annrheumdis-2013-204248. Epub 2014 Jan 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2013)
22
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2011)
20
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age of ≥18 years.
  2. Definite diagnosis of AS according to the modified New York criteria.
  3. History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each or NSAIDs intolerance/contraindication.
  4. Active disease as defined by a BASDAI value of ≥4 at screening despite concomitant treatment with an NSAID or without NSAIDs in case of intolerance/contraindication.
  5. Able and willing to give a written informed consent and comply with the requirements of the study protocol.
  6. If female: either not of child-bearing potential (menopausal since 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception.
  7. If male: either not of child-bearing potential (surgically sterilized, e.g. vasectomy) or is willing and able to practice a reliable method of contraception.
  8. If on NSAIDs: the dose must be stable for at least 2 weeks prior to baseline.
  9. If on oral steroids: the dose must not exceed 10 mg (prednisolone equivalent) per day and must be stable for at least 4 weeks prior to baseline.
  10. If on methotrexate: the dose must not exceed 25 mg per week and must be stable for at least 4 weeks prior to baseline, must be stable for 4 weeks prior to baseline.
  11. If on analgesics: the dose must be stable for at least 2 weeks prior to baseline.

Exclusion Criteria:

  1. The female subject is pregnant or lactating.
  2. Patients with other chronic inflammatory articular disease or systemic autoimmune disease.
  3. History of inadequate response to previous anti-tumor necrosis factor (TNF) α therapy.
  4. Previous treatment with biologics other than TNF α blockers.
  5. Treatment with any other investigational drug within 4 weeks of 5 half-life of the drug (whichever is longer) prior to baseline.
  6. Treatments with disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate within 4 weeks prior to screening (8 weeks for leflunomide or 4 weeks with a standard cholestyramine wash-out).
  7. Treatment with intravenous, intramuscular or intraarticular/periarticular steroids within 4 weeks prior to screening.
  8. Any active current infection, a history of recurrent clinically significant infection, infections requiring treatment with antibiotics within 4 weeks prior to baseline.
  9. Current clinical signs and symptoms suggestive for tuberculosis.
  10. Positive interferon gamma release assay (IGRA) test at screening and/or abnormal chest x-ray (performed at screening or within 3 months prior to screening) suggestive for past or present tuberculosis (positive x-ray). Patients with a positive IGRA test but negative chest x-ray and without clinical symptoms suggestive for tuberculosis may participate in the study after initiation of standard prophylactic antimycobacterial treatment.
  11. Chronic infection with hepatitis B or C, history of human immunodeficiency virus infection.
  12. Primary or secondary immunodeficiency.
  13. Actual malignancies or history of malignancies with curative treatment within 5 years prior to screening, except successfully treated non-metastatic squamous-cell or basal-cell carcinoma or carcinoma in situ of the cervix.
  14. Evidence of severe uncontrolled gastrointestinal, hepatic, renal, pulmonary, cardiovascular, nervous or endocrine disorders.
  15. Any other conditions making the patient unsuitable in the opinion of the investigator for the participation in the current study.
  16. Patients with a history of a severe psychiatric illness, which might interfere with the patient's ability to understand the requirements of the study and assessment.
  17. Diagnosis of fibromyalgia.
  18. Alcohol abuse or illegal drug consume in the last 12 months.
  19. Vaccination with a live vaccine within 12 weeks prior to baseline.
  20. Known hypersensitivity to any component of the study medication.
  21. Clinically significant laboratory abnormalities
  22. Patients who are institutionalised due to regulatory or juridical order.
  23. Patients with contraindications for the magnetic resonance imaging (MRI)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01330901
Other Study ID Numbers  ICMJE TOPAS
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party J. Sieper, Charite University, Berlin, Germany
Original Responsible Party Joachim Sieper, MD, Charite University, Berlin, Germany
Current Study Sponsor  ICMJE Charite University, Berlin, Germany
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joachim Sieper, MD Charite University, Berlin, Germany
PRS Account Charite University, Berlin, Germany
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP