E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ACTIVE AXIAL SPONDYLOARTHRITIS (AXSPA) WITHOUT X-RAY EVIDENCE OF ANKYLOSING SPONDYLITIS (AS) AND OBJECTIVE SIGNS OF INFLAMMATION |
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E.1.1.1 | Medical condition in easily understood language |
Multicenter study to evaluate efficacy and safety of Certolizumab Pegol in subjects with active inflammation in the spine with no damage on x-rays. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076297 |
E.1.2 | Term | Non-radiographic axial spondyloarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of CZP 200mg Q2W on the signs and symptoms of subjects with active axSpA without x-ray evidence of AS. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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. 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 18 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 and met the ASAS criteria for axSpA (not including family history and good response to NSAIDs; see Appendix 18.1). 6. Subjects must have had back pain for at least 12 months before Screening. 7. Subjects must NOT have sacroiliitis defined by mNY criteria (see Appendix18.2) (bilateral ≥Grade 2; unilateral ≥Grade 3) on SI joint 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. |
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E.4 | Principal exclusion criteria |
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.
9. Prior medications exclusions Subjects must not have used the following medications in the manner as detailed by the exclusion criteria in the following table in the study protocol (see Table 7‒1). 10-13. Previous clinical studies and previous biological therapy exclusions- for dettails, please refer to page 44 of the study protocol. 14-30. Medical History Exclusions- for details, please refer to pages 52- 54 of the study protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) response at Week 52 2. Axial SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 12 (this primary variable is applicable for countries where requested by regulatory authorities) 3. Certolizumab pegol plasma concentration at Baseline 4. Certolilzumab pegol plasma concentration at Week 1 5. Certolilzumab pegol plasma concentration at Week 2 6. Certolilzumab pegol plasma concentration at Week 4 7. Certolilzumab pegol plasma concentration at Week 12 8. Certolilzumab pegol plasma concentration at Week 24 9. Certolilzumab pegol plasma concentration at Week 36 10. Certolilzumab pegol plasma concentration at Week 52 11. Certolilzumab pegol plasma concentration at Follow-up Visit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.; 10. Week 52 2.; 7. Week 12 3. Baseline (Week 0) 4. Week 1 5. Week 2 6. Week 4 8. Week 24 9. Week 36 11. Follow-up Visit (8 weeks after the Week 52)
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E.5.2 | Secondary end point(s) |
1. Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) at Week 52 2. Change from Baseline to Week 12 in the Bath ankylosing spondylitis functional index (BASFI) 3. Change from Baseline to Week 52 in the Bath ankylosing spondylitis functional index (BASFI) 4. Change from Baseline to Week 12 in the Bath ankylosing spondylitis disease activity index (BASDAI) 5. Change from Baseline to Week 52 in the Bath ankylosing spondylitis disease activity index (BASDAI) 6. Change from Baseline to Week 12 in sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) score 7. Relevant changes to background medication from Baseline to Week 52 8. Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 9. Change from Baseline in ASQoL at Week 1 10. Change from Baseline in ASQoL at Week 2 11. Change from Baseline in ASQoL at Week 4 12. Change from Baseline in ASQoL at Week 12 13. Change from Baseline in ASQoL at Week 24 14. Change from Baseline in ASQoL at Week 36 15. Change from Baseline in ASQoL at Week 48 16. Change from Baseline in nocturnal spinal pain Numerical Rating Scale (NRS) at Week 52 17. Occurence of anterior uveitis (AU) or new AU flares through Week 52 18. Incidence of treatment-emergent adverse events (TEAEs) during the study 19. Incidence of serious adverse events (SAEs) during the study 20. Adverse events leading to withdrawal from investigational medicinal product (IMP) during the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 52 2.;4.;6.;12.; From Baseline to Week 12 3.;5.;7.;8.;16.;17.; From Baseline to Week 52 9: From Baseline to Week 1 10: From Baseline to Week 2 11: From Baseline to Week 4 13: From Baseline to Week 24 14: From Baseline to Week 36 15: From Baseline to Week 48 18.-20. From Baseline until Follow-up (FU)/Safety Follow-up Extension (SFE) (up to Week 60/156)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bulgaria |
Canada |
Czech Republic |
Hungary |
Poland |
Russian Federation |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |