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 | 21.1 |
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.1.2 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 | 10028395 - Musculoskeletal and connective tissue disorders |
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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 | 10002556 |
E.1.2 | Term | Ankylosing spondylitis |
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 |
• To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adult subjects with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2); • To assess the safety and tolerability of upadacitinib in subjects with active axSpA including bDMARD-IR AS (Study 1) and with nr axSpA (Study 2).
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of upadacitinib in extended treatment in adult subjects with active axSpA including bDMARD-IR AS who have completed the Double-Blind Period (Study 1) and with nr-axSpA who have completed the Double-Blind Period (Study 2).
• To evaluate the maintenance of disease control after withdrawal of upadacitinib in those who achieved ASDAS < 1.3 at Week 104 and ASDAS < 2.1 at Week 88. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• adult females and males who are at least 18 years of age • clinical diagnosis of AS who meet the modified New York Criteria for AS (Study 1); OR • clinical diagnosis of nr-axSpA fulfilling the 2009 ASAS classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS and have objective signs of active inflammation on MRI of sacroiliac joints or based on high sensitivity CRP > ULN (Study 2). • must have a BASDAI score ≥ 4 and a Patient's Assessment of Total Back Pain score ≥ 4 based on a 0 – 10 numerical rating scale at the Screening and Baseline Visits. • For Study 1, subjects must have exposed to 1 or 2 bDMARD (atleast 1 tumor necrosis factor (TNF) inhibitor or 1 interleukin [IL]-17 inhibitor) and subject must have discontinued 1 bDMARD therapy due to either lack of efficacy (after at least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance (irrespective of treatment duration). • For Study 2, prior treatment with at most 1 bDMARD (either 1 TNF inhibitor or 1 IL-17 inhibitor) is allowed in at least 20%, but not exceeding 35% of subjects) Remission-Withdrawal Period Specific Criteria: • Subject must be on study drug upon completion of the Open-Label Extension Period of Study 1 or Study 2 through Week 104. • Subject must achieve ASDAS (CRP) < 1.3 at Week 104 and ASDAS (CRP) < 2.1 at Week 88. • Subject must voluntarily sign and date an informed consent to participate in the Remission-Withdrawal Period, approved by an IEC/IRB. • Subject must not have a newly suspected/acquired medical condition and/or initiate a new medication since the last dose of study drug that would have precluded his/her enrollment into the main study. • There must be no reason the Investigator believes that the subject is an unsuitable candidate to participate in the remission-withdrawal period or receive study drug or would place the subjects at risk by continuing to participate in the study. • Subjects must be willing to keep background axSpA medications stable during the Remission-Withdrawal Period. |
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E.4 | Principal exclusion criteria |
• Subject must not have total spinal ankylosis • Subjects who have had an inadequate response to both a TNF inhibitor and IL-17 inhibitor are not eligible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Study 1 - Primary endpoint is ASAS 40 response at week 14 Study 2 - Primary endpoint is ASAS 40 response at week 14 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study 1 - Week 14 Study 2 - Week 14 |
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E.5.2 | Secondary end point(s) |
Study 1: 1. Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS); 2. Change from Baseline in magnetic resonance imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) score (spine); 3. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response; 4. ASAS20 response 5. ASDAS Inactive Disease (ASDAS score < 1.3); 6. Change from Baseline in Patient's Assessment of Total Back Pain (Total Back Pain); 7. Change from Baseline in Patient's Assessment of Nocturnal Back Pain (Nocturnal Back Pain); 8. ASDAS Low Disease Activity (ASDAS score < 2.1); 9. Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI); 10. ASAS partial remission (PR) (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS 40); 11. Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL); 12. Change from Baseline in ASAS Health Index (HI); 13. Change from Baseline in linear bath Ankylosing Spondylitis Metrology Index (BASMIlin). 14. Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES).
Study 2: 1. Change from Baseline in ASDAS; 2. Change from Baseline in MRI SPARCC score (SI joints); 3. BASDAI 50 response; 4. ASDAS Inactive Disease (ASDAS score < 1.3); 5. Change from Baseline in Patient's Assessment of Total Back Pain (Total Back Pain); 6. Change from Baseline in Patient's Assessment of Nocturnal Back Pain (Nocturnal Back Pain); 7. ASDAS Low Disease Activity (ASDAS score < 2.1); 8. ASAS PR (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS40); 9. Change from Baseline in BASFI; 10. Change from Baseline in ASQoL 11. Change from Baseline in ASAS HI. 12. ASAS20 response; 13. Change from Baseline in BASMIlin. 14. Change from Baseline in MASES. 15. ASAS40 response at Week 52 (for European Union [EU]/European Medicines Agency [EMA] regulatory purposes). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study 1 - Week 14 Study 2 - Week 14 and week 52
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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 | Yes |
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 | 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 | 2 |
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 | 92 |
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 |
Mexico |
Turkey |
Argentina |
Brazil |
Canada |
China |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Russian Federation |
Taiwan |
Ukraine |
United Kingdom |
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 | 5 |
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 | 5 |
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 |