Active Ankylosing Spondylitis

Primary objective To demonstrate the proportion of subjects on secukinumab (combined 150 mg s.c. and 300 mg s.c.) with no radiographic progression as measured by mSASSS at Week 104 is superior to subjects on GP2017 (adalimumab biosimilar 40 mg s.c.). Secondary objectives • To demonstrate the proportion of subjects on secukinumab (150 mg s.c. or 300 mg s.c.) with no radiographic progression at Week 104 is superior to subjects on GP2017 (adalimumab biosimilar 40 mg s.c.). • To demonstrate the change from baseline in mSASSS in subjects on secukinumab (150 mg s.c. or 300 mg s.c.) is superior to GP2017 (adalimumab biosimilar 40 mg s.c.) at Week 104. • To demonstrate the proportion of subjects with a syndesmophyte at baseline with no new syndesmophytes at Week 104 on secukinumab (150 mg s.c. or 300 mg s.c.) is superior to GP2017 (adalimumab biosimilar 40 mg s.c.). • To evaluate the Berlin SI joint edema score in subjects on secukinumab (150 mg s.c. and 300 mg s.c.) at Week 104 versus GP2017 (adalimumab biosimilar 40 mg s.c.) (in a subset of subjects at selected sites). • To evaluate the ASspiMRI-a Berlin modification score in subjects on secukinumab (150 mg s.c. and 300 mg s.c.) at Week 104 versus GP2017 (adalimumab biosimilar 40 mg s.c.) (in a subset of subjects at selected sites). • To evaluate ASAS 20 response, ASAS 40 response, ASAS partial remission and ASDAS inactive disease in subjects on secukinumab 150 mg s.c. compared to secukinumab 300 mg s.c. at Week 104. • Overall safety and tolerability of secukinumab.

AIN457

Secukinumab

Pre-filled syringe

150mg

Primary Outcome Measures :
No radiographic progression as measured by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) [ Time Frame: 104 weeks ]
To demonstrate the proportion of subjects on secukinumab (150 mg s.c. or 300 mg s.c.) with no radiographic progression as measured by mSASSS at Week 104 is superior to subjects on GP2017 (adalimumab biosimilar 40 mg s.c.)

Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Patient must be able to understand and communicate with the investigator and comply
with the requirements of the study and must give a written, signed and dated informed
consent before any study assessment is performed
2. Male or non-pregnant, non-lactating female patients at least 18 years of age
3. Diagnosis of moderate to severe AS with radiologic evidence (centrally read X-ray)
fulfilling the Modified New York criteria for AS (Appendix 3)
4. Active AS assessed by total BASDAI ≥ 4 (0-10) at Baseline
5. Spinal pain as measured by BASDAI question #2 ≥ 4 (0-10) at Baseline
6. Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline
7. hsCRP ≥ 5 mg/L OR presence of at least 1 syndesmophyte on centrally read spinal X-ray
 Subjects are permitted to have one hsCRP re-test during the screening period.
 Spinal X-rays obtained to confirm presence of syndesmophytes will be performed
after hsCRP results are confirmed by the central lab to be < 5 mg/L and must be
confirmed by the central imaging vendor prior to inclusion in the study.
8. Patients should have been on NSAIDs at the highest tolerated dose for at least 8 weeks
prior to randomization with an inadequate response or failure to respond, or less than 8
weeks if therapy had to be withdrawn due to intolerance, toxicity or contraindications
9. Patients who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part
of their AS therapy are required to be on a stable dose for at least 2 weeks before
randomization
10. Patients taking MTX (≤ 25 mg/week) or sulfasalazine (≤ 3 g/day) are allowed to continue
their medication and must have taken it for at least 3 months and have to be on a stable
dose for at least 4 weeks prior to randomization
11. Patients on MTX must be on stable folic acid supplementation before randomization
12. Patients who are on a DMARD other than MTX or sulfasalazine must discontinue the
DMARD 4 weeks prior to randomization
13. Patients taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day
prednisone or equivalent for at least 2 weeks before randomization

Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No
additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.
1. Patients with total ankylosis of the spine
2. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process
obtained within 3 months prior to screening and evaluated by a qualified physician
3. Previous exposure to secukinumab, adalimumab or any other biological
immunomodulating agent, including those targeting IL-17, IL-17 receptor or TNFα
4. Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine, oxycodone)
5. Use of any investigational drug and/or devices within 4 weeks of randomization, or a
period of 5 half-lives of the investigational drug, whichever is longer
6. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar
chemical classes
7. Any intramuscular corticosteroid injection within 2 weeks before randomization
8. Previous treatment with any cell-depleting therapies including but not limited to antiCD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, antiCD19)
9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive human
chorionic gonadotropin (hCG) laboratory test
10. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using effective methods of contraception during
dosing of study treatment and minimum 16 weeks or longer if local label requires it after
the last dose (e.g., 20 weeks for secukinumab, 5 months for adalimumab in EU). Effective
contraception methods include:
 Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
 Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking
investigational drug. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment
 Male sterilization (at least 6 months prior to screening). For female patients on the
study, the vasectomized male partner should be the sole partner for that subject
 Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/vaginal suppository
 Use of oral (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy
(failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking investigational drug.
In case local regulations deviate from the contraception methods listed above, local
regulations apply and will be described in the ICF.
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at
least six weeks ago. In the case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.
11. Active ongoing inflammatory diseases other than AS that might confound the evaluation
of the benefit of secukinumab or adalimumab therapy, including inflammatory bowel disease or uveitis
12. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine,
cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator
immunocompromises the patient and/or places the patient at unacceptable risk for
participation in an immunomodulatory therapy
13. Significant medical problems or diseases, including but not limited to the following:
uncontrolled hypertension (≥ 160/100 mmHg), congestive heart failure (New York Heart
Association status of class III or IV), uncontrolled diabetes, or very poor functional status
unable to perform self-care
14. History of clinically significant liver disease or liver injury as indicated by abnormal liver
function tests such as SGOT (AST), SGPT (ALT), alkaline phosphatase, or serum
bilirubin. The Investigator should be guided by the following criteria:
 Any single parameter may not exceed 2 x upper limit of normal (ULN). A single
parameter elevated up to and including 2 x ULN should be re-checked once more as
soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out lab error.
15. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum
creatinine level exceeding 1.5 mg/dL (132.6 µmol/L)
16. Screening total WBC count < 3,000/µL, or platelets < 100,000/µL or neutrophils 
1,500/µL or hemoglobin < 8.5 g/dL (85 g/L)
17. Active systemic infections during the last two weeks (exception: common cold) prior to
randomization
18. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis
infection as defined by either a positive PPD skin test (the size of induration will be
measured after 48-72 hours, and a positive result is defined as an induration of ≥ 5mm or
according to local practice/guidelines) or a positive central laboratory tuberculosis
screening test as indicated in the assessment schedule in Table 6-1. Patients with a positive
test may participate in the study if further work up (according to local practice/guidelines)
establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment according to local country guidelines
must have been initiated
19. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at
screening or randomization
20. History of lymphoproliferative disease or any known malignancy or history of malignancy
of any organ system within the past 5 years (except for basal cell carcinoma or actinic
keratoses that have been treated with no evidence of recurrence in the past 3 months,
carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed)
21. Current severe progressive or uncontrolled disease which in the judgment of the clinical
investigator renders the patient unsuitable for the study
22. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor
tolerability or lack of access to veins)
23. Inability or unwillingness to receive injections with PFS
24. Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude
the participant from adhering to the protocol or completing the study per protocol
25. Donation or loss of 400 mL or more of blood within 8 weeks before randomization
26. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before randomization
27. Patients who know they will be unable to complete 2 year study treatment period
28. Plans for administration of live vaccines during the study period or 6 weeks prior to randomization