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 | 18.1 |
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 evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in subjects with rheumatoid arthritis who were on etanercept plus methotrexate combination therapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of etanercept plus methotrexate therapy compared to methotrexate monotherapy on maintenance of remission.
To evaluate the efficacy of 1) etanercept monotherapy compared to methotrexate monotherapy and 2) etanercept plus methotrexate therapy compared to methotrexate monotherapy on:
- disease activity
- disease worsening and time to disease worsening
- remission and time to recapture remission after rescue treatment
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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 pharmacogenetic sub-study to evaluate the correlation of inherited genetic variations to rheumatoid arthritis and/or responsiveness to etanercept and methotrexate.
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E.3 | Principal inclusion criteria |
In very good RA disease control for ≥ 6 months in the opinion of the investigator
Receiving treatment with etanercept for RA for ≥ 6 months prior to run-in visit 1
Receiving treatment with methotrexate of 10 mg to 25 mg weekly for ≥ 6 months AND on a stable dose of oral methotrexate for ≥ 8 weeks prior to run-in visit 1
≥ 18 years of age at screening |
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E.4 | Principal exclusion criteria |
Subject has known history of alcoholic hepatitis, nonalcoholic steatohepatitis or immunodeficiency syndromes, including Human Immunodeficiency Virus infection.
Subject has any active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to run-in visit 1.
Subject has a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to run-in visit 1.
Subject has known alcohol addiction or dependency or uses alcohol daily.
Subject has used biologic DMARD other than etanercept OR has used an oral janus kinase inhibitor ≤ 6 months prior to run-in visit 1
Subject has known alcohol addiction or dependency or uses alcohol daily.
Subject has one or more significant concurrent medical conditions per investigator judgment
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E.5 End points |
E.5.1 | Primary end point(s) |
Simplified Disease Activity Index (SDAI) remission (≤ 3.3) |
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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. SDAI score and change from baseline at all measured timepoints
2. Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS-28-ESR) and change from baseline at all measured timepoints
3. Disease activity score (28 joint) using the C-reactive protein formula (DAS-28-CRP) and change from baseline at all measured timepoints
4. Clinical Disease Activity Index (CDAI) and change from baseline at all measured timepoints
5. SDAI remission (≤ 3.3) at all measured timepoints
6. Boolean remission at all measured timepoints
7. Disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization
8. Time to disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization
9. In subjects that receive rescue treatment:
• Time to recapture SDAI remission after starting rescue treatment
• SDAI remission at week 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All subjects:
•SDAI score, Disease activity score [DAS-28-ESR and DAS-28-CRP], Clinical Disease Activity Index, SDAI remission and Boolean remission evaluated Day 1, week 12, 24, 36 and 48 weeks.
•Disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization.
•Time to disease worsening defined as an SDAI > 3.3 and ≤ 11 during two consecutive visits at least 2 weeks apart or SDAI > 3.3 and ≤ 11 on three or more separate visits or SDAI > 11 after randomization.
In subjects that receive rescue treatment during the double-blind treatment period:
•Time to recapture SDAI remission after starting rescue treatment
•SDAI remission at week 48 |
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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 | 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 | 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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Canada |
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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End of Study will be the time when the last subject is assessed or receives an intervention for evaluation in the study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 20 |