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 |
Rheumatoid Arthritis - The most common form of inflammatory arthritis. It is a condition where your body’s immune system causes joints to become swollen and damaged. |
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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 |
Overall Aim: To determine whether a patient's baseline naive T-cell frequency can guide treatment decisions for treatment-naive early RA patients. Specifically, can we rationalise the use of MTX and offer more targeted treatment for patients with a poor prognosis based on their naive T-cells?
Primary Objective:
To determine whether the proportion of patients achieving clinical remission after first-line treatment with methotrexate and standard treat to target care differs according to naive CD4+ T-cell frequency (normal/abnormal) at baseline.
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E.2.2 | Secondary objectives of the trial |
1. To determine the proportion of patients that achieve clinical remission for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving etanercept + methotrexate compared to methotrexate with T2T care.
2. To determine whether the proportion of patients that achieve ultrasound remission (absence of inflammation on ultrasound) with first-line treatment with MTX and T2T care differs according to naïve T-cell frequency (normal/abnormal) at baseline.
3. To determine the proportion of patients that achieve ultrasound remission for patients with abnormal baseline naïve T-cell frequencies receiving etanercept + MTX compared to MTX with T2T care.
4. To determine the proportion of patients who normalize their T-cell frequency for patients with abnormal baseline naïve T-cells receiving MTX with T2T care or etanercept + MTX.
5. To determine whether patient reported outcomes differ between patients with normal or abnormal baseline naive T-cells.
6. To determine whether the prop |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has a diagnosis of RA as defined by the new ACR/EULAR 2010 classification criteria 2. Newly diagnosed (within 12 weeks) 3. Active disease at screening (DAS28ESR ≥3.2) 4. Anti-citrillunated peptide protein antibody positive (ACPA) 5. Male & female subjects ≥18 years old. 6. DMARD-naïve 7. No use of intra-muscular/Intra-articular or oral corticosteroids 4 weeks prior to screening. 8. All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives. 9. Patients must have the capacity and be willing to provide written informed consent and comply with the requirements of the protocol. 10. Subjects deemed to be in good health with respect to clinical examination and screening blood tests, including full blood count (FBC), urea and electrolytes (U&E), and liver functions tests (LFT)- See below exclusion criteria
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E.4 | Principal exclusion criteria |
1. Use of any additional investigational medications or products within 4 weeks of screening. 2. Use of intramuscular, intra-articular or oral corticosteroids within 4 weeks prior to screening. 3. Pregnant/lactating women or planning pregnancy within 24 weeks of last protocol treatment 4. Planned surgery within the study period (requiring omission of study medication > 28 days). 5. The presence of other comorbidities, which the physician deems as significant to interfere with evaluation (musculoskeletal condition such as osteoarthritis & fibromyalgia). 6. Diagnosis of another inflammatory arthritis or conective tissue disease e.g. psoriatic arthritis or Ankylosing spondylitis, primary Sjogren’s syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis. 7. Patients with any ongoing or active infection or any major episode of severe infection requiring hospitalization or treatment with IV antibiotics within the preceding 4 weeks of screening and/or orally administered antibiotics in the preceding 2 weeks of screening. 8. Any contraindication to conventional DMARD’s and anti-TNF therapy 9. In receipt of a live vaccination within 4 weeks prior to screening 10.Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by:
o Aminotransferase (AST)/alanine aminotransferase (ALT) >3x upper limit of normal (ULN), OR Bilirubin >51µmol/L
o Serum Creatinine >175 mmol/L, eGFR below 30ml/L/min/1.73m2 o Neutrophils <2000 x 10*6/L
o Platelets <125 x 109/L
o Haemoglobin <90 g/L for males and <85 g/L for females
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) at 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies. |
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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) |
• The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) after 12 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies
• The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) at 12 weeks and 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
• The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies
• The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care(Arm B) vs. etanercept + methotrexate (Arm C)
• The difference in the proportions of patients in imaging remission (PD=0) after 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) or abnormal (Arm B) naïve CD4+T-cell frequencies
• The difference in the proportions of patients in imaging remission (PD = 0) 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
• The difference in the proportion of patients with normal naïve CD4+ T-cells at 24 weeks (24 weeks)for patients with abnormal baseline naïve CD4+ T-cells receiving methotrexatewith T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
• The difference in the proportions of patients achieving sustained clinical remission (DAS28ESR ≤2.6 at both 12 and 24 weeks) (Arm A vs. Arm B and Arm B vs. Arm C)
• The difference in the average (median) cumulative amount of intramuscular corticosteroid use at 24 weeks between study arms (Arm A vs. Arm B and Arm B vs. Arm C). This will include any administered at the 24 week visit.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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) | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 all patients have completed 24 weeks of follow-up of the trial, any safety data are resolved and procedures are signed off and all analyses of laboratory samples are complete. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |