Active axial spondyloarthritis (axSpA)

Primary objective The primary objective of the study is to demonstrate the efficacy of CZP 200mg Q2W on the signs and symptoms of subjects with active axSpA without x-ray evidence of ankylosing spondylitis. Secondary objective(s) The secondary objectives of the study are to assess efficacy, safety, and tolerability and to demonstrate the effect of CZP on:  Health outcomes  Disease Activity  SI joint inflammation through MRI  Changes in concomitant and background medications

Certolizumab Pegol 200mg/ml, solution for subcutaneous injection

Certolizumab Pegol

solution for subcutaneous injection

200

The primary efficacy variable is Ankylosing Spondylitis Disease Activity Score major
improvement (ASDAS-MI) response at Week 52.

The secondary efficacy variables are Assessment in Axial SpondyloArthritis International Society 40% (ASAS40) response at Weeks 12 and 52, change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 12 and 52, change from Baseline in BASDAI at Weeks 12 and 52, change from Baseline in Sacroiliac-Spondyloarthritis Research Consortium of Canada (SI-SPARCC) score at Week 12, and the number of subjects without relevant changes to background medication.

Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written
Informed Consent form is signed and dated by the subject or legal representative.
2. The Subject/legal representative is considered reliable and capable of adhering to the
protocol (eg, able to understand and complete questionnaires), visit schedule, or medication
intake according to the judgment of the Investigator.
3. Subject is at least 20 years old at the Screening Visit.
4. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of
childbearing, or effectively practicing an acceptable method of contraception (either
oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and
spermicide). Abstinence only is not an acceptable method. Subjects must agree to use
adequate contraception during the study and for at least 10 weeks (or [for participating
countries of the EU – 5 months in accordance with the Summary of Product Characteristics,
SPC] longer if required by local regulations) after the last dose of study treatment. Male
subjects must agree to ensure they or their female partner(s) use adequate contraception
during the study and for at least 10 weeks (or [for participating countries of the
EU - 5 months in accordance with the SPC] longer if required by local regulations) after their
last dose of study treatment.
5. Subjects must have a documented diagnosis of adult-onset axSpA as defined by the specified
ASAS criteria (not including family history and good response to NSAIDs; see
Appendix 18.1) with at least 12 months symptom duration before Screening.
6. Subjects must have evidence of inflammatory back pain as defined by the ASAS criteria.
7. Subjects must NOT have sacroiliitis defined by mNY criteria (see Appendix18.2) (bilateral
≥Grade 2; unilateral ≥Grade 3) on SI x-rays (based on central reading of x-rays, within the
last 12 months from Baseline).
8. Subjects must have active disease as defined by each of the following at Screening and
Baseline:
 BASDAI score ≥4
 Spinal pain ≥4 on a 0 to 10 NRS (from BASDAI item 2)
9. Subjects must have a combination of current evidence of sacroiliitis on the screening MRI as
defined by ASAS/OMERACT scoring confirmed via central reading (MRI+) and CRP either
>upper limit of normal (ULN) or ≤ULN (for CRP the ULN is defined as the ULN indicative
for inflammatory disease) at Baseline (CRP+ or CRP-), or no evidence of sacroiliitis on the
screening MRI (MRI-) and CRP >ULN (CRP+) as follows:
 MRI+/CRP+
 MRI+/CRP-
 MRI-/CRP+
10. Subjects must have had an inadequate response to, have a contraindication to, or have been
intolerant to at least 2 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.

Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject has previously participated in this study or subject has previously been assigned to
treatment in a study of the medication under investigation in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP) (or a
medical device) within the previous 3 months (or 5 half-lives, whichever is greater) or is
currently participating in another study of an IMP (or a medical device).
3. Subject has history of chronic alcohol abuse or drug abuse within the last year.
4. 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. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as
stated in this protocol.
Axial SpA-disease-related exclusions
6. Subjects must not have AS or any other inflammatory arthritis (eg, RA, systemic lupus
erythematosus, or sarcoidosis).
7. Subject must not have fibromyalgia.
8. Subjects must not have a secondary, noninflammatory condition (eg, osteoarthritis) 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.
Prior medications exclusions
Subjects must not have used the following medications in the manner as detailed by the
exclusion criteria in the following table (see Table 7‒1).
Previous clinical studies and previous biological therapy exclusions
9. Subjects must not have received any nonbiological therapy for axSpA not listed in Table 7‒1
within or outside a clinical study in the 3 months or within 5 half-lives prior to the Baseline
Visit (whichever is longer).
10. Subjects must not have received any experimental biological agents (defined as those agents
unlicensed for use in axSpA in Europe or the USA).
11. Subjects must not have received previous treatment with a PEGylated compound that
resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
12. Subjects may not have been exposed to more than 1 TNF-antagonist prior to the Baseline
Visit and may not be a primary failure to any TNF-antagonist therapy (defined as no
response within the first 12 weeks of treatment with the TNF-antagonist).
Medical History Exclusions
13. Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study
or within 3 months following the final dose of the investigational product.
14. Subjects with a history of chronic or recurrent infections (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).
15. Subjects with a history of herpes zoster infection within 6 months prior to the Baseline Visit.
16. Subjects with known TB infection, at high risk of acquiring TB infection, or LTB infection
are excluded.
a. Known TB infection whether present or past is defined as:
i) Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or
extra-pulmonary)
ii) History of active TB infection involving any organ system or findings in other organ
systems consistent with TB infection
iii) 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:
i) Known exposure to another person with active TB infection within the 3 months prior
to Screening
ii) 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. LTB infection (unless the subject has completed a full course of prophylaxis for LTB
infection within 12 months prior to screening or appropriate prophylaxis is initiated at least
4 weeks prior to study treatment and continued to completion of prophylaxis). Please refer to
Section 12.6.3 for further details and instructions.
17. Subjects with concurrent acute or chronic viral hepatitis B or C or with human
immunodeficiency virus (HIV) infection.
18. Subjects with history of or current active infection with Histoplasma, Coccidiodes,
Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), Blastomyces, or
Aspergillus.
19. Subjects must not have a history of an infected joint prosthesis at any time.
20. 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 permitted).
21. 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).
22. Subjects with a history of a lymphoproliferative disorder including lymphoma or current
signs and symptoms suggestive of lymphoproliferative disease.
23. Concurrent malignancy or a history of malignancy (subjects with less than 3 excised basal
cell carcinomas or with cervical carcinoma in situ successfully surgically treated more than 5
years prior to Screening may be included).
24. Subjects with Class III or IV congestive heart failure as per the New York Heart Association
(NYHA) 1964 criteria.
25. Subjects with a history of, or suspected, demyelinating disease of the central nervous system
(eg, multiple sclerosis or optic neuritis).
26. Subjects having had major surgery (including joint surgery) within 8 weeks prior to
Screening, or having planned surgery within 6 months after entering the study
27. Subjects with a current or recent history, as determined by the Investigator, of severe,
progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary,
cardiac, or neurological disease.
28. Subjects with significant laboratory abnormalities, including but not limited to:
 liver function tests >2.0 x ULN, if the subject is not treated with MTX and > ULN if
subject is on concomitant MTX-treatment
 Estimated Glomerular Filtration Rate as measured by Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI; Levey et al, 2009) <60 mL/min/1.732
 white blood cell ([WBC] <3.0x109/L).
29. Subjects with any other condition which, in the Investigator’s judgment, would make the
subject unsuitable for inclusion in the study.