Ustekinumab for the Treatment of Patients With Active Ankylosing Spondylitis

NCT01330901 | Completed Phase 2

• 1 other identifier: TOPAS
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Ankylosing Spondylitis

Outcome Measures

Primary Outcomes (1)

• The Assessment of Spondyloarthritis International Society (ASAS)40 response

  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)

  week 24

Secondary Outcomes (5)

• The Assessment of Spondyloarthritis International Society (ASAS)20 response at week 24

  Week 24

• The Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement

  Week 24

• The Assessment of Spondyloarthritis International Society (ASAS) partial remission

  Week 24

• The Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement

  Week 24

• Number of participants with adverse events as a measure of safety and tolerability

  Week 28

Study Arms (1)

Ustekinumab

EXPERIMENTAL

Ustekinumab 90 mg subcutaneously at week 0, 4 and 16

Drug: Ustekinumab

Interventions

Ustekinumab DRUG

Ustekinumab 90 mg given subcutaneously at weeks 0, 4, and 16

Also known as: Stelara

Ustekinumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of ≥18 years.
• Definite diagnosis of AS according to the modified New York criteria.
• History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each or NSAIDs intolerance/contraindication.
• 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.
• Able and willing to give a written informed consent and comply with the requirements of the study protocol.
• 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.
• 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.
• If on NSAIDs: the dose must be stable for at least 2 weeks prior to baseline.
• 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.
• 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.
• If on analgesics: the dose must be stable for at least 2 weeks prior to baseline.

You may not qualify if:

• The female subject is pregnant or lactating.
• Patients with other chronic inflammatory articular disease or systemic autoimmune disease.
• History of inadequate response to previous anti-tumor necrosis factor (TNF) α therapy.
• Previous treatment with biologics other than TNF α blockers.
• Treatment with any other investigational drug within 4 weeks of 5 half-life of the drug (whichever is longer) prior to baseline.
• 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).
• Treatment with intravenous, intramuscular or intraarticular/periarticular steroids within 4 weeks prior to screening.
• Any active current infection, a history of recurrent clinically significant infection, infections requiring treatment with antibiotics within 4 weeks prior to baseline.
• Current clinical signs and symptoms suggestive for tuberculosis.
• 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.
• Chronic infection with hepatitis B or C, history of human immunodeficiency virus infection.
• Primary or secondary immunodeficiency.
• 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.
• Evidence of severe uncontrolled gastrointestinal, hepatic, renal, pulmonary, cardiovascular, nervous or endocrine disorders.
• Any other conditions making the patient unsuitable in the opinion of the investigator for the participation in the current study.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Department of Rheumatology, Charité - Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Related Publications (2)

• Parthasarathy R, Santiago F, McCluskey P, Kaakoush NO, Tedla N, Wakefield D. The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies. Trends Microbiol. 2023 Feb;31(2):142-158. doi: 10.1016/j.tim.2022.08.008. Epub 2022 Sep 1.

  PMID: 36058784 DERIVED

• 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.

  PMID: 24389297 DERIVED

Related Links

• Official web site of the study center

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joachim Sieper, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: April 5, 2011
• First Posted: April 7, 2011
• Study Start: October 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

DE (1)