E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pragmatic trial baricitinib versus First biological in “Tight Control” Patients suffering from Rheumatoid Arthritis (PERFECT) |
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E.1.1.1 | Medical condition in easily understood language |
Baricitinib in the treatment of patients suffering from Rheumatoid Arthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
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 demonstrate non-inferiority of a T2T strategy in which conventional synthetic disease modifying drugs (csDMARDs) refractory RA patients are initially treated with tsDMARD baricitinib versus the comparable T2T strategy in which patients are initially treated with a biological tumor necrosis factor inhibitor (TNFi) in a pragmatic randomized trial. |
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E.2.2 | Secondary objectives of the trial |
• To test for superiority of baricitinib first versus TNFi biological first in csDMARDs refractory RA patients in terms of ACR response, in case of noninferiority of baricitinib first. • To evaluate safety of baricitinib versus biological (TNFi) first in csDMARDs refractory RA patients. • To compare time to first remission and time to persistent remission between treatment arms. • To compare radiographic outcomes between treatment arms. • To compare patient reported outcomes between treatment arms. • To perform a cost effectiveness analysis in which both treatment strategies are compared.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Clinical diagnosis of RA • Active disease (DAS28> 3.2 ) • Former treatment according to T2T principles, at the discretion of the attending rheumatologist, i.e. past treatment decisions informed by disease activity measurements • Previous use of at least one csDMARD
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E.4 | Principal exclusion criteria |
• Disease duration >5 years • Previous treatment with any biological DMARD or tsDMARD • Contraindication for either TNFi or baricitinib • Latent or active tuberculosis • Active or recurrent infections • 3x upper limit of normal ALAT • GFR < 30 ml/min. • Failure to provide written informed consent • Refusal to use effective contraceptive during the study period
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is non-inferiority of baricitinib first versus TNFi first in terms of ACR50 response at 12 weeks |
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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) |
Secondary endpoints include ACR20, 50, and 70 across measurement points, the percentage of patients achieving sustained SDAI remission, time to first SDAI remission, radiographic progression, health economics, safety, and change from baseline in DAS28 score and patient-reported outcomes (PROMs). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Days 2-7, week 4, week 8, week 12, week 24, week 36, 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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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When the last patient has completed the last clinical assessment, questionnaires and the last X-ray of the hands and feet at week 48. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |