E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
early unclassified arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Joint inflammation with unknown cause |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062164 |
E.1.2 | Term | Seronegative 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 Objectives: … to establish - which is the best strategy to ensure early remission (within 3 months) of early unclassified arthritis (UA): early treatment with MTX or baricitinib or delayed treatment in case spontaneous remission does not occur within 3 months. - which is the best strategy to achieve cure (or sustained drug free remission) of recent onset UA: early treatment with MTX or baricitinib
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E.2.2 | Secondary objectives of the trial |
To establish - which is the best treatment, MTX or baricitinib, to ensure rapid symptom relief of recent onset undifferentiated arthritis -which is the best treatment to prevent (or delay) progression of early unclassified arthritis to rheumatoid arthritis -which is the best treatment in terms of patients’ (in)tolerance of medication and reported side effects and drug toxicity over time -which is the best treatment to ensure optimal functional ability over time -which is the best treatment in terms of patients’ satisfaction with treatment after 3 months on NSAIDs, MTX or baricitinib -which is the best option in patients who achieve remission on baricitinib: stop baricitinib as soon as remission is achieved, or continue for 6 more months to prevent relapse
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- ≥18 year of age and able to give written informed consent (in Dutch or English) and fill out questionnaires in Dutch (or English version, if available) - Clinical early unclassified arthritis of at least one joint, not fulfilling ACR/EULAR 2010 criteria for rheumatoid arthritis - Symptom duration of arthritis <1 year - Other diagnoses causing the arthritis rejected (including infection, (pseudo-)gout, psoriatic arthritis, non-rheumatoid auto-immune disease, paraneoplastic arthritis) - DAS>1.6 - No wish to become pregnant, breastfeed or father a child during the study - No contraindications to treatment with NSAIDs, MTX (or sulfasalazine or leflunomide as alternative) and baricitinib as required in the study |
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E.4 | Principal exclusion criteria |
- Alcohol or substance abuse - Immuno-compromised state either based on co-morbidity or co-medication - Leucopenia <3*10^9/l, and/or neutropenia <1*10^9/l - Hemoglobin <5 mmol/l - Increased liver enzymes > 3x upper limit of normal - Renal insufficiency with estimated creatinine clearance <40% - Interstitial lung disease as seen on X-thorax - Maintenance treatment with corticosteroids exceeding prednisone 10 mg daily or equivalent - Active or ongoing chronic infection, (recurrent) serious infection(s) in past 4 months, latent TB who refuse anti-tuberculous treatment, hepatitis B with positive DNA viral load or hepatitis C with positive RNA viral load, patients with anti-HB2 and anti-HBc antibodies who refuse monitoring of hepatitis B DNA expression - Increased tendency to develop arterial or venous thrombosis. Assessed by the treating rheumatologist based on family history and medical history of the patient. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of patients in early clinical remission (Definition of clinical remission: DAS<1.6 by independent assessor, or DAS>1.6 by independent assessor but no clinical arthritis according to treating rheumatologist) - Percentage of patients in sustained drug free remission (at least 6 consecutive months in clinical remission without DMARD and corticosteroids)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Percentage of patients in early clinical remission at 3 months. Percentage of patients in sustained drug free remission at 18 months. |
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E.5.2 | Secondary end point(s) |
Disease Activity Score (DAS) based on a 44 swollen joint count including a 53 joint Ritchie Articular Index. Functional ability as measured by the Health Assessment Questionnaire (HAQ) Physical and emotional wellbeing as measured by the ShortForm-36 (SF-36) Functional ability in preferred activities as measured by the MACTAR Quality of life as measured by the EuroQol 5-dimensional questionnaire (EQ-5D) Neuropathic pain as measured by the PainDETECT questionnaire (PDQ) Illness perception as measured by the IPQ-K (brief illness perception questionnaire) Toxicity as defined by number and severity of adverse events based on routine laboratory tests as required for study medications, open end questioning during study visits, and interim reports of adverse events Local joint pain as measured on a 100 mm Visual Analogue Scale (VAS), measuring from 0 (no pain) to 100 (maximum imaginable pain) General fatigue as measured on a 100 mm VAS (no to maximum) Morning stiffness as measured on a 100 mm VAS (no to maximum) General functional disability as measured on a 100 mm VAS (no to maximum) General satisfaction with medication use (convenience) as measured on a 100 mm VAS (no to maximum). General dissatisfaction with medication use as measured on a 100 mm VAS (no to maximum). The extent to which benefits of medication use are more important than downsides as measured on a 100 mm VAS (no to maximum). Disease activity as assessed by the treating rheumatologist on a 100 mm VAS at 3 months and 12 months and over time. Feelings of depression as measured with the Beck’s Depression Inventory. Time to clinical remission from baseline and per drug (MTX or baricitinib) from start of treatment Time to clinical improvement (by patient diary and clinical assessments at weeks 2,4 and 8) Progression to classifiable RA (2010 criteria) over time from baseline Time to flare (from absence of any arthritis to at least one joint with active arthritis) (Progression of) radiologic damage as measured with the Sharp-vanderHeijde Score (baseline, 6, 12 and 18 months).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, week 2, week 4, week 8 and then 3-monthly up to 18 months follow-up: DAS, HAQ, SF36, VAS scales, treatment satisfaction, clinical remission, RA classification, time to flare Baseline, 3 months, 18 months: MACTAR, EQ-5D, Beck's Depression Inventory, Baseline, week 2, 3 months, 18 months: PainDETECT week 2, week 4, week 8 and then 3-monthly up to 18 months follow-up: toxicity Baseline, week 2, week 4, week 8: time to clinical improvement Baseline, 6, 12 and 18 months: Sharp-vanderHeijde Score |
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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 | No |
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) | 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 | Yes |
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 | 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 | 12 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |