E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Radiographic Axial Spondyloarthritis |
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E.1.1.1 | Medical condition in easily understood language |
A chronic inflammatory condition affecting the spine and sacroiliac joint. It is characterized by pain and stiffness of joints. |
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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 | 10041672 |
E.1.2 | Term | Spondylitis ankylosing |
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 or 80 mg every 4 weeks) vs placebo in tumor necrosis factor inhibitor (TNFi) experienced patients with active radiographic axial spondyloarthritis (r-axSpA) at Week 16. |
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E.2.2 | Secondary objectives of the trial |
To compare both ixekizumab regimens (80 mg every 2 weeks or 80 mg every 4 weeks) to placebo at Week 16 on signs and symptoms, function, mobility, and quality of life in TNFi experienced patients with r-axSpA. |
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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 |
There is a MRI substudy that will be conducted in selected countries. Patients will have MRIs of the spine at screening and at Week 16. The MRI addendum version is 23Nov2015.
MRI addendum countries:
Germany, Korea, Mexico, Italy, Poland, The Netherlands, Canada, US |
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E.3 | Principal inclusion criteria |
-Are at least 18 years of age
-Have an established diagnosis of radiographic axial spondyloarthritis (r-axSpA) with sacroiliitis defined
radiographically according to the mNY criteria
-Patients have a history of back pain ≥3 months with age at onset <45 years.
-Have had prior treatment with at least 1 and not more than 2 TNF inhibitors.
-Must have had an inadequate response 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.
-Have given written informed consent |
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E.4 | Principal exclusion criteria |
- Have total ankylosis of the spine
-Have taken none or more than two tumor necrosis factor inhibitor medications
- Have recently received a live vaccine within 12 weeks or have had a vaccination with Bacillus Calmette-Guerin (BCG) within the past year.
- Have an ongoing or serious infection within the last 12 weeks or evidence of active tuberculosis
- Have a compromised immune system.
- Have any other serious and/or uncontrolled diseases.
- Have either a current diagnosis or a recent history of malignant disease.
- Have had Major surgery within 8 weeks of baseline, or will require surgery during the study
- Are pregnant or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response. |
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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) |
-Proportion of patients achieving an ASAS20 response
-Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
-Proportion of patients achieving Bath Ankylosing
Spondylitis Disease Activity Index 50 (BASDAI50) response
-Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
-Proportion of patients achieving ASDAS inactive disease
-Change from baseline in Short Form 36 (SF-36) physical component score (PCS)
-Change from baseline in ASAS Health Index (ASAS HI)
-Change from baseline in magnetic resonance imaging (MRI) of the spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] –Berlin score). (This endpoint applies to MRI addendum only). |
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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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Brazil |
Canada |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Puerto Rico |
Spain |
United Kingdom |
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 | 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 |