Protocol Title : A Randomised, open labelled study in anti ... - EME
Protocol Title : A Randomised, open labelled study in anti ... - EME
Protocol Title : A Randomised, open labelled study in anti ... - EME
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<strong>Protocol</strong> Version 3 14/01/2013<br />
optimised. Together we will construct B-cell immunoglobul<strong>in</strong> VH genes libraries pre- and posttreatment<br />
for exhaustive repertoire and clonality analysis evaluated us<strong>in</strong>g Roche 454 next<br />
generation sequenc<strong>in</strong>g (NGS) technology. Clonal identity pre- and post treatment would clearly<br />
<strong>in</strong>dicate that repopulation occurs from escaped clones with<strong>in</strong> the synovial tissue and the need for<br />
disrupt<strong>in</strong>g-destroy<strong>in</strong>g such survival niches aim<strong>in</strong>g for remission us<strong>in</strong>g alternative therapeutics<br />
currently be<strong>in</strong>g developed <strong>in</strong> cancer such us BTK and/or proteasome <strong>in</strong>hibitors.<br />
5.14 End of Study Def<strong>in</strong>ition<br />
The end of the <strong>study</strong> will be triggered when the last patient completes their f<strong>in</strong>al <strong>study</strong> visit (48<br />
month assessment).<br />
5.15 Subject Withdrawal<br />
Participants may be withdrawn if they are <strong>in</strong>tolerant to the therapeutic product, experience toxicity<br />
related side-effects or <strong>in</strong>tercurrent illness necessitat<strong>in</strong>g cessation of the therapy with<strong>in</strong> 6 months of<br />
recruitment.<br />
Specifically, the follow<strong>in</strong>g criteria will necessitate premature withdrawal of a <strong>study</strong> participant:<br />
- Suspected progressive multifocal leukoencephalopathy (PML)<br />
- ALT or AST > 5 x ULN<br />
- ANC < 1.5 x 10^9/ l<br />
- Platelet count < 75 x 10^3/μl<br />
- Receipt of live vacc<strong>in</strong>es<br />
- Pregnancy<br />
Subjects may withdraw consent for any reason at any time without prejudice to there normal care.<br />
Patients withdraw<strong>in</strong>g from the <strong>study</strong> will cont<strong>in</strong>ue to be monitored and managed with<strong>in</strong> their rout<strong>in</strong>e<br />
Rheumatology cl<strong>in</strong>ic by their named consultant.<br />
5.16 Data Collection and Follow up for Withdrawn Subjects<br />
Participants who are withdrawn will be asked to cont<strong>in</strong>ue to have 6 monthly follow up visits (i.e. 6 /<br />
12 / 18 24 months from recruitment). If this is not acceptable patients will have an early withdrawal<br />
visit and their current disease activity<br />
6 PHARMACOVIGILANCE<br />
6.1 Adverse Event (AE)<br />
An AE is any untoward medical occurrence <strong>in</strong> a subject to whom a medic<strong>in</strong>al product has been<br />
adm<strong>in</strong>istered, <strong>in</strong>clud<strong>in</strong>g occurrences which are not necessarily caused by or related to that product.<br />
An AE can therefore be any unfavourable and un<strong>in</strong>tended sign (<strong>in</strong>clud<strong>in</strong>g an abnormal laboratory<br />
f<strong>in</strong>d<strong>in</strong>g), symptom or disease temporarily associated with the use of an Investigational Medic<strong>in</strong>al<br />
Product (IMP), whether or not considered related to the IMP.<br />
6.2 Adverse Reaction (AR)<br />
An AR is any untoward and un<strong>in</strong>tended response <strong>in</strong> a subject to an Investigational Medic<strong>in</strong>al<br />
Product (IMP), which is related to any dose adm<strong>in</strong>istered to that subject. All adverse events<br />
judged by either the report<strong>in</strong>g <strong>in</strong>vestigator or the Sponsor as hav<strong>in</strong>g a reasonable causal<br />
relationship to a medic<strong>in</strong>al product qualify as adverse reactions. The expression reasonable causal<br />
relationship means to convey <strong>in</strong> general that there is evidence or argument to suggest a causal<br />
relationship.<br />
6.2.1 Serious Adverse Event (SAE) or Serious Adverse Reaction (SAR)<br />
An SAE fulfils at least one of the follow<strong>in</strong>g criteria:<br />
Is fatal – results <strong>in</strong> death (NOTE: death is an outcome, not an event)<br />
Is life-threaten<strong>in</strong>g<br />
Requires <strong>in</strong>patient hospitalisation or prolongation of exist<strong>in</strong>g hospitalisation<br />
Results <strong>in</strong> persistent or significant disability/<strong>in</strong>capacity<br />
Study: R4RA EudraCT: 2012-002535-28 29 / 34