Ustekinumab for the Treatment of Patients With Active Ankylosing Spondylitis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01330901
• Date of registration: 05/04/2011
• Prospective Registration: Yes
• Primary sponsor: Charite University, Berlin, Germany
• Public title: Ustekinumab for the Treatment of Patients With Active Ankylosing Spondylitis TOPAS
• Scientific title: UsTekinumab for the Treatment Of Patients With Active Ankylosing Spondylitis (TOPAS) - a 28-week, Prospective, Open-label, Proof-of-concept Study
• Date of first enrolment: October 2011
• Target sample size: 22
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01330901
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Germany

Contacts

• Name: Joachim Sieper, MD
• Affiliation: Charite University, Berlin, Germany

Key inclusion & exclusion criteria

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) a
therapy.

4. Previous treatment with biologics other than TNF a 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis

Intervention(s)

Drug: Ustekinumab

Primary Outcome(s)

The Assessment of Spondyloarthritis International Society (ASAS)40 response [Time Frame: week 24]

Secondary Outcome(s)

The Assessment of Spondyloarthritis International Society (ASAS)20 response at week 24 [Time Frame: Week 24]

Number of participants with adverse events as a measure of safety and tolerability [Time Frame: Week 28]

The Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement [Time Frame: Week 24]

The Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement [Time Frame: Week 24]

The Assessment of Spondyloarthritis International Society (ASAS) partial remission [Time Frame: Week 24]

Secondary ID(s)

TOPAS

Source(s) of Monetary Support

Please refer to primary and secondary sponsors