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 | 19.0 |
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 |
The purpose of this study is to assess the efficacy of ustekinumab, in adult participants with active radiographic axial spondyloarthritis (AxSpA), who are naive to anti-TNF alpha agents, as measured by the reduction in signs and symptoms of radiographic AxSpA. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the effect of treatment with ustekinumab in anti-TNFα naïve subjects with active radiographic AxSpA on the following:
-Efficacy related to improving physical function, range of motion, health-related quality of life, and other health outcomes.
-Safety.
-Pharmacokinetics (PK) and immunogenicity. |
|
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 |
-Pharmacogenomic study
-Microbiome study
-MRI |
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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 atbaseline, as evidenced by both a BASDAI score of greater than 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 Creactive
protein (hsCRP) level of >=0.300 milligram per deciliter (mg/dL) at Screening
-If using nonsteroidal antiinflammatory drugs (NSAIDs) or other analgesics for
AS, must be on a stable dose for at least 2 weeks prior to the first
administration of study agent. If currently not using NSAIDs or other analgesics
for AS, must not have received NSAIDs or other analgesics for AS for at least
2 weeks prior to the first administration of the study agent
-A woman of childbearing potential must have a negative serum (betahuman
chorionic gonadotropin [betahCG]) at screening and |
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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 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 prior biologic therapy, including but not
limited to antiTNF alpha agents, tocilizumab, alefacept, efalizumab,
natalizumab, abatacept, anakinra, ustekinumab, tidrakizumab or other antiinterleukin (IL) 23 biologics, brodalumab, secukinumab, ixekizumab, and Bcell
depleting therapies
-Participants who have received any systemic immunosuppressives or
diseasemodifying 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 chloroquine, azathioprine, cyclosporine, mycophenolate
mofetil, gold, and penicillamine
-Participant who have received leflunomide within 3 months prior to the first
administration of study agent (irrespective of undergoing a drug elimination
procedure), or have received leflunomide within 12 months prior to the first
administration of study agent and have not undergone a drug elimination
procedure |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants Achieving an Assessment of SpondyloArthritis International Society (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) |
-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.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 | 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 10 |
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 |
Czech Republic |
Korea, Republic of |
Mexico |
Poland |
Russian Federation |
Taiwan |
Ukraine |
United States |
|
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
|
|
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 |