E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis (RA) |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid 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 |
• To compare the efficacy of ABT-494 QD versus placebo, and versus adalimumab (ADA) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in subjects with moderately to severely active RA who are on a on a stable background of methotrexate (MTX) and who have an inadequate response to MTX (MTX-IR).
• To compare the efficacy of ABT-494 QD versus placebo for the prevention of structural progression in RA subjects with moderately to severely active RA who are on a on a stable background of MTX and who have an inadequate response to MTX (MTX-IR).
• To compare the safety and tolerability of ABT-494 QD versus placebo, and versus ADA in subjects with moderately to severely active RA subjects who are on a stable background of MTX and who have an inadequate response to MTX (MTX-IR).
• To evaluate the long-term safety, tolerability, and efficacy of ABT-494 in subjects with RA. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult male or female, at least 18 years old.
• Diagnosis of RA for ≥ 3 months.
• Subjects must have been on oral or parenteral MTX therapy ≥ 3 months prior to the first dose of study drug.
• At least one of the following at Screening: ≥ 3 bone erosions on x-ray OR ≥ 1 bone erosion and a positive rheumatoid factor OR ≥ 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
• Subjects with prior exposure to at most one bDMARD (except ADA) may be enrolled (up to 20% of total study population)
• Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
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E.4 | Principal exclusion criteria |
• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib). Subjects who are considered inadequate responders to bDMARD therapy
• History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects achieving ACR20 response at Week 12 / the proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12 |
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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) |
• Change from baseline in modified Total Sharp Score (mTSS) at Week 26
• Proportion of subjects achieving LDA at Week 12
• Change from baseline in Disease Activity Score (DAS) 28(CRP) at Week 12
• Change from baseline in Health Assessment Questionnaire (HAQ-DI) at Week 12
• ACR50 response at Week 12
• ACR70 response at Week 12
• Proportion of subjects achieving LDA based on DAS28 (CRP) ≤ 3.2 at Week 12
• Change from baseline in Short Form 36 (SF-36) PCS at Week 12
• Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 12
• Proportion of subjects with no radiographic progression at Week 26
• Change from baseline in Work Stability Scale for Rheumatoid Arthritis (RA-WIS) at Week 12
• Change from baseline in morning stiffness (severity) at Week 12
- Change from baseline in morning stiffness at Week 12 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 158 |
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 |
Australia |
Belarus |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Colombia |
Egypt |
European Union |
Hong Kong |
Israel |
Kazakhstan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Puerto Rico |
Russian Federation |
Serbia |
Singapore |
South Africa |
Taiwan |
Turkey |
Ukraine |
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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LVLS or last 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 | 6 |
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 | 6 |