E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis |
Reumatoïde artritis |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis |
Reumatoïde artritis |
|
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 |
The primary objective is to investigate the association between quantitative changes in whole body F-18-PEG Folate PET/CT (Folate PET) after 4 weeks and clinical response to anti-TNF therapy at 26 weeks of treatment in patients with clinically active established |RA. |
Het primaire doel is om de associatie tussen kwantitatieve veranderingen in F-18-PEG folaat PET / CT (folaat PET) na 4 weken en klinische respons op anti-TNF-therapie na 26 weken behandeling bij patiënten met klinisch actieve RA te onderzoeken. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to relate quantitative Folate PET outcome after 4 weeks to histological changes in synovial tissue after 4 weeks of anti-TNF treatment (with a particular focus on macrophage infiltration and FRβ expression). |
Het secundaire doel is om de kwantitatieve Folaat PET-uitkomst na 4 weken te relateren aan histologische veranderingen in synoviaal weefsel na 4 weken anti-TNF-behandeling (met een specifieke focus op infiltratie van macrofagen en FRβ-expressie). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must be at least 30 years of age
• Diagnosis of rheumatoid arthritis according to the 1987 revised criteria of the American Rheumatism Association (ARA)13 and/or the 2010 ACR/EULAR Rheumatoid Arthritis classification criteria.
• Patients with clinically active disease as assessed by a physician; with arthritis in at least one knee or ankle joint and have a clinical indication to start with anti-TNF (either Infliximab, Etanercept, Adalimumab or Certolizumab)
• Prior treatment with one anti-TNF agent is permitted, but may not be a primary failure to any anti-TNF agent (defined as no response within the first 12 weeks of treatment)
• Treatment with disease modifying anti-rheumatic drugs (DMARDS) and oral corticosteroid up to 10 mg daily is allowed, provided that there is a stable dose for at least 4 weeks prior to inclusion and during the study up to 12 weeks of follow up.
• Non-steroidal anti-inflammatory drugs (NSAID) is permitted, provided that there is a stable dose for at least 4 weeks prior to inclusion and during the study up to 12 weeks of follow up.
• Patients must be able to adhere to the study appointments and other protocol requirements
• Patients must be capable of giving informed consent and the consent must have been obtained prior to the study related procedures. |
• Patienten moeten 30 jaar of ouder zijn.
• Diagnose vanreumatoïde artritis volgens de 1987 gereviseerde criteria van de American Rheumatism Association (ARA)13 en/of de 2010 ACR/EULAR Rheumatoid Arthritis classificatie criteria.
• Patienten met klinisch actieve ziekte zoals bepaald door een arts; met artritis in ten minste één knie of enkel gewricht en die een klinische indicatie hebben om te starten met anti-TNF(Infliximab, Etanercept, Adalimumab of Certolizumab).
• Eerdere behandeling met één anti-TNF middel is toegestaan, maar mag niet primair gefaald hebben op een anti-TNF middel (gedefinieerd als geen respons binnen de eerste 12 weken van therapie).
• Behandeling met disease modifying anti-rheumatic drugs (DMARDS) en orale corticosteroïden tot 10 mg per dag is toegestaan, mits er in de maand voorafgaand aan inclusie en in de eerste 12 weken van de studie een stabiele dosis gebruikt wordt.
• Non-steroidal anti-inflammatory drugs (NSAID) zijn toegestaan, mits er in de maand voorafgaand aan inclusie en in de eerste 12 weken van de studie een stabiele dosis gebruikt wordt.
• Patienten moeten in staat zijn om zich te houden aan studie afspraken en andere protocol verplichtingen.
• Patienten moeten in staat zijn om een geïnformeerde keuze te maken over deelname aan het onderzoek, en moeten toestemming geven voor start van het onderzoek. |
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E.4 | Principal exclusion criteria |
• Use of intramuscular or intravenous corticosteroids within 4 weeks prior to screening.
• Patients who received methotrexate and folic acid less than 7 days before tracer injection.
• Treatment with any investigational drug within the previous 3 months
• Known pregnancy or breast feeding
• Research related radiation exposure (cumulative ≥5 mSv) in the year before inclusion |
• Het gebruik van intramusculaire of intraveneuze corticosteroïden binnen 4 weken voorafgaand aan de screening.
• Patiënten die minder dan 7 dagen vóór tracer-injectie methotrexaat en foliumzuur toegediend kregen.
• Behandeling met onderzoeksmedicatie in de afgelopen 3 maanden
• Bekende zwangerschap of het geven van borstvoeding
• Onderzoeksgerelateerde blootstelling aan straling (cumulatief ≥5 mSv) in het jaar voorafgaand aan inclusie. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The association between quantitative changes in Folate PET after 4 weeks of anti-TNF treatment and clinical response to therapy up to 26 weeks of treatment in patients with established RA. Clinical follow-up up to 26 weeks will be regarded as golden standard. |
De associatie tussen de kwantitatieve veranderingen in folaat PET tracer opname in gewricht(en) na 4 weken van anti-TNF behandeling en klinische respons op therapie tot 26 weken van behandeling bij patiënten met gevestigde reumatoïde artitis. Klinische follow-up na 26 weken van behandeling wordt beschouwd als gouden standaard. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The association between quantitative Folate PET tracer uptake in joint(s) and histological changes in synovial tissue over 4 weeks of anti-TNF treatment (with particular focus on macrophage infiltration, FRβ expression and macrophage polarization status). |
De associatie tussen de kwantitatieve folaat PET tracer opname in gewrichten en histologische veranderingen in synoviaal weefsel na 4 weken anti-TNF behandeling (met bijzondere aandacht voor de infiltratie van macrofagen, FRβ-expressie en macrofaagpolarisatiestatus). |
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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 | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 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 | 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 | |