E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Psoriatic Arthritis |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
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 |
Primary Objective 1. To compare the efficacy of upadacitinib 15 mg QD and 30 mg QD versus placebo and versus adalimumab (ADA) for the treatment of signs and symptoms of PsA in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). Secondary Objective 2. To compare the efficacy of upadacitinib 15 mg QD and 30 mg QD versus placebo for the prevention of structural progression in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). 3. To compare the safety and tolerability of upadacitinib 15 mg QD and 30 mg QD versus placebo and versus adalimumab in subjects with moderately to severely active PsA who have an inadequate response or intolerance to 1 or more non-biologic DMARD (DMARD-IR). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term safety, tolerability and efficacy of ABT-494 15 mg QD and 30 mg QD in subjects with PsA who have completed Period 1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age 2. Diagnosed with psoriatic arthritis with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) 3. Subject has active disease at Baseline defined as ≥ 3 tender joints (based on 68 joint counts) and ≥ 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits 4. Diagnosis of active plaque psoriasis or documented history of plaque psoriasis 5. Subject is on current treatment with ≤ 2 nonbiologic DMARDs 6. Subject has had an inadequate response to previous or current treatment with at least 1 non-biologic DMARD (MTX, SSZ, LEF, cyclosporine, apremilast, bucillamine, or iguratimod), or subject has an intolerance to or contraindication for DMARDs 7. Presence of either at Screening: • ≥ 1 erosion on x-ray • hs-CRP > laboratory-defined upper limit of normal (ULN) |
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E.4 | Principal exclusion criteria |
1. Prior exposure to any Janus Kinase (JAK) inhibitor 2. Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than MTX, SSZ, LEF, apremilast, HCQ, bucillamine, or iguratimod; or use of MTX in combination with LEF. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects achieving ACR20 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) |
1. Change from baseline in HAQ-DI 2. Proportion of subjects achieving a static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline 3. Psoriasis Area Severity Index (PASI) 75 response (for subjects with ≥ 3% BSA psoriasis at baseline) 4. Change from baseline in modified PsA Sharp/van der Heijde Score (SHS) 5. Proportion of subjects achieving Minimal Disease Activity (MDA) 6. Proportion of subjects with resolution of enthesitis (LEI = 0) 7. ACR 20 response rate (non-inferiority of upadacitinib vs adalimumab); 8. Change from baseline in SF-36 PCS 9. Change from baseline in FACIT-Fatigue Questionnaire at Week 12; 10. ACR 20 response rate (superiority of upadacitinib vs adalimumab); 11. Proportion of subjects with resolution of dactylitis (LDI = 0) 12. Change from baseline in Patient's Assessment of Pain NRS (superiority of upadacitinib vs. adalimumab); 13. Change from baseline in HAQ-DI (superiority of upadacitinib vs. adalimumab); 14. Change from baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire 15. ACR 50/70 response rate 16. ACR 20 response rate |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 12 2. Week 16 3. Week 16 4. Week 24 5. Week 24 6. Week 24 7. Week 12 8. Week 12 9. Week 12 10. Week 12 11. Week 24 12. Week 12 13. Week 12 14. Week 16 15. Week 12 16. Week 2
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 84 |
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 |
Chile |
Colombia |
Egypt |
Malaysia |
New Zealand |
Singapore |
Switzerland |
Bosnia and Herzegovina |
Ukraine |
Hong Kong |
Korea, Democratic People's Republic of |
Puerto Rico |
Taiwan |
Australia |
Belarus |
Brazil |
Canada |
China |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
South Africa |
United Kingdom |
United States |
Türkiye |
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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 subjects' last visit or the actual date of follow-up contact, whichever is later. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |