A Multicentre, 12 Week Double Blind Placebo Controlled Randomized Study of Etanercept on a Background NSAID in the Treatment of Adult Subjects with Non Radiographic Axial
Spondyloarthritis with a 92 Week Open Label Extension

1. Diagnosis of axial spondyloarthritis, as defined by the ASAS criteria. Duration of symptoms of >3 months and <5 years at the time of consent (Appendix 1).
2. Active symptoms defined by a BASDAI *4.
3. Axial symptoms of back pain with a less than favorable response to current intake of an NSAID at optimal tolerated dose as determined by the investigator. Subjects must have failed at least 2 NSAIDs (including the current one) taken separately at the optimal tolerated dose with a total combined duration of >4 weeks.
4. Subject must be taking a stable dose of an NSAID for at least 14 days before baseline.
5. Female or male 18 years or older but less than 50 years at the time of consent.
6. In the opinion of the investigator, subject is a reasonable candidate for treatment with
etanercept.
7. No contraindication to MRI examination (metal implants or inability to lay flat for 30-60 minutes for example).
8. Negative serum pregnancy test taken at screening, negative urine pregnancy test taken at baseline and serum pregnancy test collected at baseline (Section 4.3 Lifestyle Guidelines).
9. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or post menopausal to use a highly effective method of birth control for the duration of the study (Section 4.3 Lifestyle Guidelines).
10. Ability to self-inject drug or have a designee who can do so.
11. Ability to store injectable test article under refrigerated conditions.
12. Demonstrates an adequate screening for tuberculosis (TB) in accordance with local country guideline.
13. Subject is able to complete health outcomes assessments and test article diary.

1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Any previous treatment with a tumor necrosis factor-alpha (TNF *) inhibitor, B/T cell inhibitor or other biologic or immunosuppressive agent for a condition other than IBD
3. Subject is currently being treated or had previous treatment within 6 months for IBD with any tumor necrosis factor-alpha (TNF *) inhibitor or any other immunosupressant.
4. Any orthopedic or medical condition that can cause chronic back pain (different than SpA) such as spondylodiscitis, tumor or advance discopathy.
5. Evidence of IBD flare within 6 months of baseline.
6. Evidence of current or recent episodes of uveitis within 6 months of baseline.
7. Radiological sacroiliitis grade is 3-4 unilaterally or grade *2 bilaterally as defined by the NY criteria (Appendix 2).
8. Subject has a known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds related to this class of medication.
9. Subject has concurrent treatment with more than 1 NSAID within 14 days at baseline.
10. Subject has a dose of NSAID that changed within 14 days before baseline.
11. DMARDS other than methotrexate, sulfasalazine and hydroxychloroquine within 4 weeks of baseline.
12. Subject has had a dose of prednisone >10 mg/day (or equivalent) or has had a dose changed within 4 weeks before baseline.
13. Subject has received an intra-articular, intravenous, intramuscular, or subcutaneous (SC) corticosteroid within 4 weeks before baseline.
14. Subject is a pregnant or breastfeeding woman.
15. Has current or recent (within 2 years of screening) active TB infection.
* Local country guidelines should be followed for appropriate TB screening in the setting of anti-TNF therapy, including a minimum of a chest radiograph and objective TB testing such as purified protein derivative [PPD] or Quantiferon depending on what is acceptable per local guidelines.
16. Untreated latent TB.
* Subjects with known latent TB infection may be allowed only if local guidelines are followed for prophylactic therapy and if TB chemoprophylaxis has been adequately completed or initiated at least 4 weeks prior to screening.
17. Received TB chemoprophylaxis during screening and has had ALT and/or AST >2x upper limit of normal [ULN] during this period.
* For subjects that have been diagnosed with TB and started chemoprophylaxis during the screening period, additional blood samples for ALT and AST must be drawn between 3- 4 weeks after initiating chemoprophylaxis. The results need to be reviewed prior to randomization.
18. Serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 1 month before test article administration.
19. Active infection at the time of the screening visit and/or the baseline visit. Certain minor active infections (ie, vaginitis, tinea, etc) could be allowed on a case by case basis only after approval from the study physician clinician.
20. Participation in other studies with a therapeutic active component within 3 months before the current study begins and/or during study participation. (Participation in non-interventional or retrospective studies might be permitted following consultation with the Pfizer Clinical team.)
21. Planned elective surgery during Period 1.
22. Subject received any live vaccines (attenuated vaccines) within 4 weeks before baseline.
23. Subject is illiterate.
24. Subject has an abnormal hematology or blood chemistry profile during the screening period. Refer to Section 6.6 for management of exclusionary lab values at baseline.
* White blood cell (WBC) count *3.5 x 109/L;
* Hemoglobin level *85 g/L or *5.3 mmol/L;
* Hematocrit *27%;
* Platelet count *125 x 109/L;
* Serum creatinine level *175 µmol/L (*1.98 mg/dL);
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level *2 times the laboratory*s upper limit of normal.
25. Subject has any clinically relevant concurrent medical conditions, including:
* Known history or presence of acute or chronic hepatitis B or hepatitis C or HIV infection; (If required by Health Authorities, an HIV test must be performed at a local lab during screening. Results of this test will be used to determine eligibility.)
* Uncompensated congestive heart failure, or class III or IV heart failure defined by the New York Heart Association classification;
* Uncontrolled hypertension (defined as screening systolic blood pressure >160 mm Hg or screening diastolic blood pressure >100 mm Hg);
* Myocardial infarction within 12 months before the screening visit;
* Coronary artery by pass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) within 12 months before the baseline visit;
* Unstable angina pectoris within 6 months before the screening visit;
* Severe pulmonary disease requiring recurrent hospitalizations or supplemental oxygen;
* Presence or history of confirmed blood dyscrasias;
* Diagnosis of multiple sclerosis or other central or peripheral nervous system demyelinating diseases;
* Presence or history of cancer (or carcinoma in situ) other than resected cutaneous basal cell or squamous cell carcinoma;
* Uncontrolled diabetes mellitus;
* Diagnosis of rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or polymyositis;
* Open cutaneous ulcers;
* Liver cirrhosis or fibrosis;
* Other severe acute or chronic medical or psychiatric condition, substance abuse or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.