E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Arthralgia of hands or feet of patients that are suspect to progress to reumatoid arthritis according to the treating rheumatologist and because of subclinical inflammation on MRI of hands and feet (Clinical Suspect Artralgia CSA) |
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E.1.1.1 | Medical condition in easily understood language |
Arthralgia of hands or feet of patients that are suspect to progress to RA according to the treating rheumatologist and with subclinical inflammation on MRI (Clinical Suspect Artralgia CSA) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
1.This study will determine the efficacy of intervention with antirheumatic treatment in the preclinical phase of RA in preventing the progression from subclinical joint inflammation in patient with clinically suspect arthralgia to clinically apparent persistent arthritis. |
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E.2.2 | Secondary objectives of the trial |
2.To characterise the efficacy of DMARD treatment on the regression of MRI features of inflammation (synovitis, bone marrow edema, tenosynovitis) and on symptoms of arthralgia 3.To characterise immune and inflammatory responses in patients with subclinical MRI inflammation without clinical arthritis before, during and after therapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years 2. Patients without clinically detectable arthritis but with arthralgia of small hand or feet joints of recent-onset (<1 year) that according to the rheumatologist is suspect to be an early presentation of RA (this symptom complex is called Clinically Suspect Arthralgia, CSA) 3. Extremity MRI positive for subclinical inflammation. 4. Ability and willingness to give written informed consent and to comply with the requirements of the study protocol
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E.4 | Principal exclusion criteria |
1. Symptoms or signs making diagnoses other than RA more likely. These are amongst others >6 tender points or Heberden or Bouchard nodules (the presence of such characteristics preclude CSA) 2. Presence of, or history of, clinically apparent arthritis (this precludes CSA) 3. Previous or current treatment with DMARDs or corticosteroids (this precludes CSA) 4. Contra indications for MRI: certain metal implants, pacemakers, GFR<30 ml/min. 5. Pregnancy or the wish to become pregnant, breast feeding 6. Bone marrow hypoplasia 7. Elevated hepatic enzyme levels (ASAT, ALAT >3 times normal value) 8. Serum creatinine level >150 umol/l or estimated clearance of <60% 9. Serious infections such as hepatitis, pyelonefritis in the past three months or chronic infectious disease such as chronic chest infections with bronchiectasis
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint The primary end point is the frequency of clinically detectable arthritis fulfilling the 2010 criteria for RA or of unclassified arthritis with a SJC of ≥2 joints, both persisting for at least 4 weeks, obtained after 2 years.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
evaluation of endpoints every 4 months during 2 years |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are: •Percentage of patients in DMARD-free sustained remission after 2 years (DMARD-free sustained remission is the persistent absence of clinically detectable synovitis) •Percentage of patients with symptom reduction (more than 2 points on 5 point Likert scale) •Functional ability measured using health assessment questionnaires (HAQ) •Change in quality of life •Work loss (absenteeism), presenteeism, work related financial loss •Changes in Sharp van der Heijde scores on hand and foot radiographs •Adverse events •Cost-efficacy
Exploratory endpoints •Reduction in MRI inflammation compared to the baseline MRI •Signatures of immune responses (such as characteristics of the ACPA response and other post-translational modifications such as anti-carbamylated protein antibodies) and inflammatory responses as defined through the analysis of serum and peripheral blood cell subsets (RNA expression profiling) and proteomics.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
evaluation of endpoints every 4 months during 2 years |
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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 | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |