E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis (RA) patients who are on Etanercept (ETN) treatment and are in remission or in a Low Disease Activity (LDA) state |
|
E.1.1.1 | Medical condition in easily understood language |
Study comparing the effect on disease activity when reducing or discontinuing Etanercept in subjects with Rheumatoid Arthritis (RA) (DOSERA) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 |
|
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 effect on disease activity of the combination of ETN 50 mg QW plus methotrexate (MTX) to placebo plus MTX over 48 weeks in RA subjects who at study start are in remission or LDA state with combination therapy with ETN 50mg weekly plus MTX |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the effect on disease activity of the combination of ETN 25 mg QW plus MTX to
a. combination of ETN 50 mg QW plus MTX
b. placebo plus MTX
over 48 weeks in RA subjects who at study start are in remission or LDA state with combination therapy with ETN 50mg weekly plus MTX.
2. To compare the change in modified Total Sharp Score (mTSS) over 48 weeks among the treatment groups.
3. To compare the change in MRI findings over 12 weeks among the treatment groups. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for the Open-label Period (Period 1):
Subject must meet all of the following conditions in order to be enrolled in the study:
1. Men and women have a diagnosis of RA based on the ACR Revised Criteria for RA.
2. Subject has a current DAS28 ≤3.2.
3. Subject is currently receiving treatment with sc ETN, either 25 mg BW or 50 mg QW, for a minimum of 14 months at baseline
4. Subject is currently receiving oral, sc or im MTX, 7.5 mg/week to 25 mg/week and at a stable dose for a minimum of 4 months at baseline.
Inclusion Criteria for the Double-Blind Randomized Period (Period 2)
1. Subject has completed open-label period 1 and has had DAS28 ≤ 3.2 at all visits during period 1 and at randomization.
|
|
E.4 | Principal exclusion criteria |
Exclusion Criteria for the Open-Label Period (Period 1)
1· Subject has earlier had an attempt of discontinuing ETN for reasons of remission or LDA state.
2. Subject has received any disease-modifying anti-rheumatic drug (DMARD), other than MTX, a dose of prednisone (or equivalent) >7.5 mg/day or has received ia, iv, im, or sc corticosteroid within one month before baseline.
Exclusion Criteria for the Double-Blind Randomized Period 2
1. Subject has used prohibited concomitant medication in period 1 or has not attended all visits in Period 1.
For additional criteria, see protocol |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who are non-failures at Week 48. These subjects are still in Period 2 at study end, which means they have not fulfilled predefined failure criteria during the study. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Proportion of subjects who are non-failures at Week 48 |
|
E.5.2 | Secondary end point(s) |
In the three treatment arms:
1. Time from randomization to failure, according to predefined criteria.
2. Proportion of subjects in remission or LDA state at each visit.
3. Proportion of time subjects are in remission or LDA state
4. Change in DAS28 at each visit.
5. Change in tender and swollen joint counts at each visit.
6. Change in physician global assessments, subject global assessments, patient global health VAS, patient pain VAS and morning stiffness at each visit.
7. Changes in ESR and CRP at each visit.
8. Change in mTSS at week 48.
9. Change in MRI findings at week 12.
10. Correlation between clinical assessment, serum biomarkers, MRI (at randomization and week 12) and X-ray findings at randomization and whether individuals have had treatment failure or not. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Time from randomization to failure.
• Proportion of subjects in remission or LDA state at each visit.
• Proportion of time subjects are in remission or LDA state
• Change in DAS28 at each visit.
• Change in tender and swollen joints at each visit.
• Change in physician global assessments, subject global assessments, patient general health VAS, patient pain VAS and morning stiffness at each visit.
• Changes in ESR and CRP at each visit.
• Change in mTSS at week 48.
• Change in MRI findings at week 12.
• Correlation between clinical assessment, serum biomarkers, MRI and X-ray findings at randomization and whether individuals have had treatment failure or not. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | No |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Patients who fail during the trial will enter into an open-label phase |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Denmark |
Finland |
Hungary |
Iceland |
Norway |
Sweden |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |