E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071400 |
E.1.2 | Term | Axial spondyloarthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
Percentage of Participants Achieving an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24 |
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E.2.2 | Secondary objectives of the trial |
-Percentage of Participants Achieving an ASAS 20 Response at Week 24 -Percentage of Participants who Achieve at Least 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 -Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 -Percentage of Participants who Achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) (CRP) Inactive Disease at Week 24 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
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E.3 | Principal inclusion criteria |
Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met - Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greaterthan or equal to (>=4) and a visual analog scale (VAS) score for total back pain of >=4, each on a scale of 0 to 10 - Participants with elevated high sensitivity C-reactive protein (hsCRP) level of >=0.300 milligram per deciliter (mg/dL) at screening - Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent - Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs. - Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population |
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E.4 | Principal exclusion criteria |
- Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease - Participants who have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration - Participants who have ever received golimumab - Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent - Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects who achieve an ASAS 40 response at Week 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To control for multiplicity for the primary endpoint analysis and the major secondary endpoint analyses, the 4 major secondary analyses listed below will be performed sequentially contingent upon the success of the primary statistical analysis in that treatment group comparison. Otherwise, the p-values for the subsequent endpoints will be considered as supportive analyses. The following prespecified order will be used to analyze the major secondary endpoints. -The proportion of subjects who achieve an ASAS 20 at Week 24. -The proportion of subjects who achieve at least a 50% improvement from baseline in BASDAI at Week 24. -The change from baseline in BASFI at Week 24. -The proportion of subjects who achieve ASDAS (CRP) inactive disease (<1.3) at Week 24. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
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 | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 |
Argentina |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Korea, Republic of |
Mexico |
Poland |
Portugal |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 37 |