Multicenter, open-label study to assess the effects of Certolizumab Pegol on the reduction of anterior uveitis flares in axial spondyloarthritis subjects with a history of anterior uveitis (C-view)

The study population will be subjects *18 years, with a documented diagnosis of adult onset axSpA as meeting the Assessment of SpondyloArthritis International Society ([ASAS] criteria of at least 3 months* symptom duration, and with active disease defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) *4, and spinal pain *4 on a 0 to 10 Numerical Rating Scale (NRS). Nonradiographic axSpA subjects must either have C Reactive Protein > upper limit of normal (ULN) and /or current evidence of sacroiliitis on Magnetic Resonance Imaging taken within 3 months prior to Baseline (no confirmation by central reading) as defined by ASAS criteria and ankylosing spondylitis subjects must have evidence of sacroiliitis on an x-ray taken within 12 months prior to Baseline meeting modified New York criteria according to the Investigator. Subjects must have a documented history of AU diagnosed by an ophthalmologist and have at least 2 AU flares in the past, of which at least 1 AU flare was in the last 12 months prior to Baseline.
Additionally, subjects must be HLA-B27 positive (if known prior to Screening, no additional testing is to be performed; if unknown, testing is to be performed at Screening and checked at Baseline) and subjects must have been intolerant to or had an inadequate response to at least 2 Nonsteroidal Anti-inflammatory drugs (NSAIDs). Inadequate response to an NSAID is defined as lack of response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the administered NSAID.

1. The subject has previously participated in this study or has previously received CZP treatment in or outside of another clinical study. However rescreening is possible if prophylactic treatment for latent tuberculosis infection (LTBI) was to be given but the Screening Period exceeded the 12 weeks.
2. The subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 3 months or is currently participating in another study of an IMP (or a medical device).
3. The subject has a history of chronic alcohol or drug abuse.
4. The subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject*s ability to participate in this study.
5. The subject has a known hypersensitivity to any components of CZP or a history of an adverse reaction to polyethylene glycol.
Axial SpA-disease related exclusions
6. Subjects must not have any other inflammatory arthritis (eg, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, or fibromyalgia).
7. Subjects must not have a secondary, noninflammatory condition that, in the Investigator*s opinion, is symptomatic enough to interfere with evaluation of the effect of study drug on the subject*s primary diagnosis of axSpA.
Ophthalmic exclusion criteria
8. Any history of uveitis (eg, posterior, panuveitis) except for AU associated with axSpA.
9. Any condition or complicating factor that may interfere with the AU assessment, for example:
a. History of cataract surgery within 6 months prior to Baseline
b. Corneal or lens opacity
c. Proliferative or severe nonproliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy
d. Neovascular/wet age-related macular degeneration
e. History of scleritis
f. History of intraocular surgery, with the exception of phacoemulsification
10. Subject has Retisert® or Iluvien® (glucocorticosteroid implant) within 3 years prior to the Baseline Visit or has had complications related to the device. Subject has had Retisert or Iluvien (glucocorticosteroid implant) removed within 90 days prior to the Baseline Visit or has had complications related to removal of the device.
11. Subject has received intraocular or periocular corticosteroids within 90 days prior to the Baseline visit.
12. Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline Visit.
13. Subject on cyclophosphamide within 30 days prior to the Baseline Visit.
14. Subject has received intravitreal methotrexate within 90 days prior to the Baseline Visit.
15. Subject has received intravitreal anti-vascular endothelial growth factor therapy:
a. Within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab)
or
b. Within 60 days of the Baseline visit for anti-VEGF Trap Zaltrap® (aflibercept)
Prior medications exclusions
16. Subjects must not have used the following medications in the manner as detailed by the exclusion criteria in Table 6-1 (protocol page 31).
Previous clinical studies and previous biological therapy exclusions
17. Subjects must not have received any nonbiological therapy for axSpA not listed in Table 1 within or outside of a clinical study in the 3 months or within 5 half lives prior to the Baseline Visit (whichever is longer).
18. Subjects must not have received any experimental biological agents (defined as those agents unlicensed for use in axSpA in the EU or the USA).
19. Subjects must not have received previous treatment with a PEGylated compound that resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
20. Subjects must not have been exposed to more than one TNF antagonist prior to the baseline visit and may not be a primary failure to any tumor necrosis factor (TNF) antagonist therapy (defined as no response within the first 12 weeks of the TNF antagonist treatment).
Medical history exclusions
21. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 5 months (or longer, if required by local regulation) following the final dose of the investigational product.
22. Subjects with a history of chronic or recurrent infections, excluding uveitis (more than 3 episodes requiring antibiotics or antivirals during the preceding year), recent serious or life*threatening infection within the 6 months prior to the Baseline Visit (including hospitalization for any infection in the last 6 months or any current sign or symptom that may indicate an infection).
23. Subjects with a history of herpes zoster infection within 6 months prior to the Baseline Visit.
24. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or LTBI.
a. Known TB infection whether present or past is defined as:
o Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or extrapulmonary)
o History of active TB infection involving any organ system or findings in other organ systems consistent with TB infection
o Any evidence by radiography or other imaging modalities consistent with previously active TB infection that is not reported in the subject*s medical history.
b. High risk of acquiring TB infection is defined as:
o Known exposure to another person with active TB infection within the 3 months prior to Screening
o Time spent in a healthcare delivery setting or institution where individuals infected with TB are housed and where the risk of transmission of infection is high.
c. Latent TB infection (unless appropriate prophylaxis is initiated prior to study treatment and continued to completion of prophylaxis) is defined as
o The absence of signs, symptoms (ie, evidence of organ-specific involvement), or physical findings suggestive of TB infection with a positive interferon-gamma release assay (IGRA; or 2 indeterminate IGRA test results) and a chest x-ray (or other imaging) without evidence of TB infection. If the result of the IGRA is indeterminate, the particular IGRA test previously performed may be repeated once; if positive or indeterminate on retest, the subject may not be randomized to study medication without further evaluation, treatment, and discussion with Study Physician, if LTBI is identified. (If active TB is identified, subject must undergo appropriate study-specified withdrawal procedures.) The retest must be done during the protocol-defined Screening window.
Note: If available, respiratory or other specimens must also be smear and culture negative for TB (Centers for disease control diagnosis of LTBI, http://www.cdc.gov/TB/topic/testing/default.htm)
Detailed information on TB definition, clinical signs, diagnosis, documentation, and treatment will be available in this protocol.
25. Subjects with current acute or chronic viral hepatitis B or C or with human immunodeficiency virus (HIV) infection.
26. Subjects with current or a history of active infection with Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, or Aspergillus.
27. Subjects with a history of an infected joint prosthesis at any time.
28. Subjects receiving any live (includes attenuated) vaccination within the 8 weeks prior to Baseline (eg, inactivated influenza and pneumococcal vaccines are allowed, but nasal influenza vaccination is not allowed).
29. Subjects who in the Investigator*s opinion have a high risk of infection (eg, subjects with leg ulcers, indwelling urinary catheter, persistent or recurrent chest infections, and subjects who are permanently bedridden or wheelchair bound).
30. Subjects with a history of a lymphoproliferative disorder, including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
31. Current malignancy or a history of malignancy (although subjects with less than 3 completely excised basal cell carcinomas or with cervical carcinoma in situ successfully surgically treated more than 5 years prior to Screening may be included).
32. Subjects with Class III or IV congestive heart failure as per the New York Heart Association 1964 criteria.
33. Subjects with a history of, or suspected, demyelinating disease of the central nervous system (eg, multiple sclerosis or optic neuritis).
34. Subjects who have had major surgery (including joint surgery) within 8 weeks prior to Screening, or have planned surgery within 6 months of the Screening Visit.
35. Subjects with a history of or a current, as determined by the Investigator, severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, or neurological disease.
36. Subjects with significant laboratory abnormalities at Screening including but not limited to:
o Liver function tests >2.0 x upper limit of normal
o Estimated Glomerular Filtration Rate<60 mL/min/1.732 as measured by Chronic Kidney Disease Epidemiology Collaboration (Levey et al, 2009)
o White blood cell count <3.0x109/L.
37. Subjects with any other condition which, in the Investigator*s judgment, would make the subject unsuitable for inclusion in the study