E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
bDMARD Naive Patients with Nonradiographic Axial Spondyloarthritis |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory disease affecting the spine and sacroiliac joint. X-ray evidence of sacroiliitis may or may not be present. |
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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 |
Compare both ixekizumab regimens (80 mg every 2 weeks [Q2W] or 80 mg every 4 weeks [Q4W]) versus placebo in patients with active nonradiographic axial spondyloarthritis (nonrad-axSpA) at Week 16 |
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E.2.2 | Secondary objectives of the trial |
To compare both ixekizumab regimens (80 mg Q2W or 80 mg Q4W versus placebo in patients with active nonrad-axSpA at Week 16 and Week 52 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Presence of sacroiliitis on MRI (according to ASAS/OMERACT criteria and based on central reading) (Rudwaleit et al. 2009d) and have at least 1 SpA feature
OR
Are positive for HLA-B27 and have at least 2 additional SpA features, according to the ASAS criteria (Sieper et al. 2009; Rudwaleit et al. 2009a) SpA features listed in Appendix 5
Patients have a history of back pain ≥3 months with age at onset <45 years.
Have active nonrad-axSpA defined as BASDAI ≥4 and total back pain ≥4 on a NRS at screening and baseline (Sieper et al. 2009)
Patients have objective signs of inflammation by presence of sacroiliitis on MRI (as defined by ASAS/OMERACT) or presence of elevated CRP (defined as CRP >5.00 mg/L).
Must have had an inadequate response, as determined by the investigator, to 2 or more NSAIDs at the therapeutic dose range for a total duration of at least 4 weeks OR have a history of intolerance to NSAIDs
Patients must have a history of prior therapy for axSpA of at least 12 weeks prior to screening. Examples of prior therapy may include but are not limited to physical therapy and NSAID treatment.
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E.4 | Principal exclusion criteria |
Fulfillment of the modified New York (mNY) criteria (van der Linden et al. 1984) with sacroiliitis defined radiographically, based on central reading: sacroiliitis grade ≥2 bilaterally or grades 3 to 4 unilaterally
Have a history of other systemic inflammatory diseases that might confound the evaluations of benefit from ixekizumab therapy (such as, but not limited to, lupus, vasculitis, or RA), or other chronic pain conditions (such as but not limited to fibromyalgia)
Note: Patients with psoriasis who do not require systemic treatment, such as, but not limited to, oral agents or biologic therapies, can be included provided these patients fulfill the study entry criteria.
Have active Crohn’s disease (CD) or active ulcerative colitis (UC)
Note: Patients may be enrolled if they have had a history of inflammatory bowel disease (IBD), including CD and UC, but have had no exacerbation for ≥6 months prior to baseline, and, if currently on treatment, must be on stable treatment for ≥6 months prior to baseline.
Have evidence of active anterior uveitis (an acute episode) within the last 42 days prior to baseline randomization
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving an ASAS40 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 16 (for regulatory agencies that require Week 16 as the primary
endpoint)
Week 52 (for regulatory agencies that require week 52 as the primary
endpoint)
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E.5.2 | Secondary end point(s) |
• Change from baseline in (ASDAS) at Week 16
• Change from baseline in ASDAS at Week 52
• Change from baseline in (BASFI) at Week 16
• Change from baseline in BASFI at Week 52
• Proportion of patients achieving ASDAS inactive disease at Week 16
• Proportion of patients achieving ASDAS inactive disease at Week 52
• Change from baseline in MRI of the (SIJ) [SPARCC] score) at Week 16
• Percent of patients without clinically meaningful changes in background therapy at Week 52
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 16 and 52 depending on the end points. See above. |
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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 | No |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Austria |
Brazil |
Canada |
Czech Republic |
Finland |
Germany |
Japan |
Korea, Democratic People's Republic of |
Mexico |
Netherlands |
Poland |
Puerto Rico |
Romania |
Russian Federation |
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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last visit or last scheduled procedure for the last patient |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |