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 objective of this study is to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week (eow) subcutaneously (SC) in maintaining remission in subjects with non-radiographic axial Spondyloarthritis (nr-axSpA). |
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E.2.2 | Secondary objectives of the trial |
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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 |
Optional Blood Sample Collection Sub-Study, 15th January 2015. Objectives: To collect samples to learn more about non-radiographic axial spondyloarthritis (nr ax SpA) response to adalimumab, as well as individual variability in response to adalimumab |
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E.3 | Principal inclusion criteria |
Main Inclusion:
- Adult subjects with inadequate response to >/= 2 non-steroidal anti-inflammatories (NSAIDs)
- Subject with axial SpA fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria
- Subject with evidence of active inflammation in the SI joints or spine on MRI, or elevated hs-CRP
-Negative Tb screening assessment
- Negative purified protein derivative (PPD) test and Chest X-Ray performed at Baseline Visit must be Negative
- Ability to administer subcutaneous injections
- General good health otherwise |
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E.4 | Principal exclusion criteria |
Main Exclusion:
- Prior anti-TNF therapy
- Fulfillment of modified New York criteria for Ankylosing Spondylitis
- Recent infection requiring treatment
- Significant medical events or conditions that may put patients at risk for participation
- Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study
- History of cancer, except successfully treated skin cancer
- Recent history of drug or alcohol abuse |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who do not experience a flare by Week 68 of the study where a flare is defined as having any 2 consecutive study visits with ASDAS ≥ 2.100. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The proportion of participants who do not experience a flare by Week 68 of the study where a flare is defined as having any 2 consecutive study visits with ASDAS ≥ 2.100. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Variable(s)
At 12 weeks after initiation of Rescue Therapy, week 28 and week 68
● ASDAS Inactive Disease (ASDAS < 1.300)
● ASDAS Major Improvement (a change from baseline ≤ –2.000)
● ASDAS Clinically Important Improvement (a change from baseline ≤ –1.100)
● ASAS20, ASAS40, ASAS 5/6 and ASAS Partial Remission
● ASAS20 response: improvement of ≥ 20% and absolute improvement of ≥ 1 unit (on a scale of 0 to 10) from Baseline in ≥ 3 of the following 4 domains, with no deterioration in the remaining domain (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit)
● Patient's Global Assessment – Represented by the PTGA-disease activity NRS score (0 to 10)
● Pain – Represented by the patient’s assessment of total back pain NRS score (0 to 10)
● Function – Represented by the BASFI NRS score (0 to 10)
● Inflammation – Represented by the mean of the 2 morning stiffness related BASDAI NRS scores (mean of items 5 and 6 of the BASDAI [0 to 10])
● ASAS40 response: improvement of ≥ 40% and absolute improvement of ≥ 2 units (on a scale of 0 to 10) from Baseline in ≥ 3 of the 4 domains above in ASAS20 with no deterioration in the potential remaining domain
● ASAS partial remission: absolute score of < 2 units for each of the 4 domains identified above in ASAS20
● ASAS5/6 response: 20% improvement from Baseline in 5 out of the following 6 domains: BASFI, patient's assessment of total back pain, PTGA-disease activity, inflammation (mean of items 5 and 6 of the BASDAI]) lateral lumbar flexion from BASMI, and hs-CRP
● Bath AS Disease Activity Index 50 (BASDAI50) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 12 weeks after initiation of Rescue Therapy, week 28 and week 68 |
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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 | Yes |
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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 |
Brazil |
Canada |
Mexico |
New Zealand |
Norway |
Puerto Rico |
Russian Federation |
Switzerland |
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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the last 70 day follow-up call |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |