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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4.4 IMP Stability<br />
Rituximab<br />
RIituximab solutions for <strong>in</strong>fusion may be stored at 2 -8 o C (36-46 o F) for 24 hours. RIituximab<br />
solutions for <strong>in</strong>fusion have been shown to be stable for an additional 24 hours at room<br />
temperature. However, s<strong>in</strong>ce Rituximab solutions do not conta<strong>in</strong> a preservative, diluted solutions<br />
should be stored refrigerated (2-8 o C) with temperature log. No <strong>in</strong>compatibilities between Rituximab<br />
and polyv<strong>in</strong>ylchloride or polyethylene bags have been observed.<br />
Tocilizumab<br />
All Tocilizumab vials must be stored at a controlled temperature of 2-8°C, and handled accord<strong>in</strong>g to<br />
GMP and GCP procedures. The <strong>in</strong>fusion bag of Tocilizumab <strong>in</strong> sal<strong>in</strong>e may be made up with<strong>in</strong> 24<br />
hours of dos<strong>in</strong>g and must be stored <strong>in</strong> a refrigerator at 2-8°C, provided the site takes precautions<br />
to prepare the <strong>in</strong>fusion aseptically. A temperature log must be kept, on which the storage<br />
temperature of the Tocilizumab and <strong>in</strong>fusion bags is recorded at least once a day.<br />
4.5 Prior and Concomitant Anit-Rheumatic Therapies<br />
Patients Enrolled <strong>in</strong>to this <strong>study</strong> will have received <strong>anti</strong>-TNF therapy <strong>in</strong> accordance with NICE<br />
guidel<strong>in</strong>es. Patients may also have received or cont<strong>in</strong>ue to receive Disease Modify<strong>in</strong>g Anti-<br />
Rheumatic Drugs (DMARD’s). If patients must be stable on 1 or more DMARDS for at least 4<br />
weeks prior to <strong>study</strong> commencement. Patients may also receive corticosteriod therapy but at a<br />
steady does for at least 4 weeks prior to recruitment.<br />
4.6 Dose modification/reduction/ delay<br />
Adherence to the planned dose regimen of <strong>study</strong> medication is required unless an adjustment is<br />
necessary for safety reasons. For patients receiv<strong>in</strong>g Tocilizumab 8 mg/kg dur<strong>in</strong>g the period of this<br />
<strong>study</strong>, the dose may be lowered to 4 mg/kg to manage safety events.<br />
5 STUDY PROCEDURES<br />
!<br />
5.1 Informed Consent Procedures<br />
Written <strong>in</strong>formed consent will be obta<strong>in</strong>ed from each patient by the pr<strong>in</strong>cipal <strong>in</strong>vestigator or<br />
designee. Informed consent will be prepared accord<strong>in</strong>g to NRES and <strong>study</strong> sponsor requirements<br />
for <strong>in</strong>formed consents. Patients who are candidates for the <strong>study</strong> must sign an <strong>in</strong>formed consent<br />
prior to any <strong>study</strong>-specific procedures be<strong>in</strong>g performed, <strong>in</strong>clud<strong>in</strong>g any <strong>study</strong> specific screen<strong>in</strong>g<br />
procedures<br />
5.2 Screen<strong>in</strong>g Procedures<br />
Patients may be screened up to 6 weeks prior to recruitment. Prior to screen<strong>in</strong>g patients will sign a<br />
<strong>study</strong> specific consent form. Screen<strong>in</strong>g will entail evaluation of <strong>in</strong>clusion and exclusion criteria,<br />
cl<strong>in</strong>ical exam<strong>in</strong>ation DAS 28 assessment, <strong>study</strong> safety blood (FBC, Ig, UE, LFT, ESR, CRP) and<br />
TB screen<strong>in</strong>g accord<strong>in</strong>g to local guidel<strong>in</strong>es.<br />
5.3 Randomization Procedures<br />
Patients will be stratified (3 strata based on B cells) and randomised with<strong>in</strong> blocks (1:1), with<br />
random block size of 6 and 4. Allocated treatment will be revealed by database once eligibility has<br />
been confirmed and patient is entered <strong>in</strong>to trial.<br />
The local pr<strong>in</strong>cipal <strong>in</strong>vestigator/research nurse will log-<strong>in</strong> to a secure web application (app) and<br />
confirm patient eligibility before they can randomise. The web app will check eligibility and<br />
subsequently allocate a randomisation number (<strong>study</strong> number). This ensures that neither the<br />
patient nor the cl<strong>in</strong>ician can choose whether or not to enter a trial depend<strong>in</strong>g on the next allocation.<br />
This part of the randomisation system will be written by the Cancer Prevention Trial Unit (CPTU)<br />
Database Programmer. The randomisation list will be prepared by the CPTU Statistician and<br />
securely embedded with the application code so that it is not accessible to end users or anyone<br />
other than the Database Programmer and a limited number of <strong>in</strong>formation support staff who have<br />
access to all systems. Once a participant has been allocated a treatment, there is an audit trail that<br />
prevents anyone from chang<strong>in</strong>g the allocation or pretend<strong>in</strong>g that no allocation had been made.<br />
Study: R4RA EudraCT: 2012-002535-28 21 / 34