Protocol Title : A Randomised, open labelled study in anti ... - EME

4.4 IMP Stability
Rituximab
RIituximab solutions for infusion may be stored at 2 -8 o C (36-46 o F) for 24 hours. RIituximab
solutions for infusion have been shown to be stable for an additional 24 hours at room
temperature. However, since Rituximab solutions do not contain a preservative, diluted solutions
should be stored refrigerated (2-8 o C) with temperature log. No incompatibilities between Rituximab
and polyvinylchloride or polyethylene bags have been observed.
Tocilizumab
All Tocilizumab vials must be stored at a controlled temperature of 2-8°C, and handled according to
GMP and GCP procedures. The infusion bag of Tocilizumab in saline may be made up within 24
hours of dosing and must be stored in a refrigerator at 2-8°C, provided the site takes precautions
to prepare the infusion aseptically. A temperature log must be kept, on which the storage
temperature of the Tocilizumab and infusion bags is recorded at least once a day.
4.5 Prior and Concomitant Anit-Rheumatic Therapies
Patients Enrolled into this study will have received anti-TNF therapy in accordance with NICE
guidelines. Patients may also have received or continue to receive Disease Modifying Anti-
Rheumatic Drugs (DMARD’s). If patients must be stable on 1 or more DMARDS for at least 4
weeks prior to study commencement. Patients may also receive corticosteriod therapy but at a
steady does for at least 4 weeks prior to recruitment.
4.6 Dose modification/reduction/ delay
Adherence to the planned dose regimen of study medication is required unless an adjustment is
necessary for safety reasons. For patients receiving Tocilizumab 8 mg/kg during the period of this
study, the dose may be lowered to 4 mg/kg to manage safety events.
5 STUDY PROCEDURES
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5.1 Informed Consent Procedures
Written informed consent will be obtained from each patient by the principal investigator or
designee. Informed consent will be prepared according to NRES and study sponsor requirements
for informed consents. Patients who are candidates for the study must sign an informed consent
prior to any study-specific procedures being performed, including any study specific screening
procedures
5.2 Screening Procedures
Patients may be screened up to 6 weeks prior to recruitment. Prior to screening patients will sign a
study specific consent form. Screening will entail evaluation of inclusion and exclusion criteria,
clinical examination DAS 28 assessment, study safety blood (FBC, Ig, UE, LFT, ESR, CRP) and
TB screening according to local guidelines.
5.3 Randomization Procedures
Patients will be stratified (3 strata based on B cells) and randomised within blocks (1:1), with
random block size of 6 and 4. Allocated treatment will be revealed by database once eligibility has
been confirmed and patient is entered into trial.
The local principal investigator/research nurse will log-in to a secure web application (app) and
confirm patient eligibility before they can randomise. The web app will check eligibility and
subsequently allocate a randomisation number (study number). This ensures that neither the
patient nor the clinician can choose whether or not to enter a trial depending on the next allocation.
This part of the randomisation system will be written by the Cancer Prevention Trial Unit (CPTU)
Database Programmer. The randomisation list will be prepared by the CPTU Statistician and
securely embedded with the application code so that it is not accessible to end users or anyone
other than the Database Programmer and a limited number of information support staff who have
access to all systems. Once a participant has been allocated a treatment, there is an audit trail that
prevents anyone from changing the allocation or pretending that no allocation had been made.
Study: R4RA EudraCT: 2012-002535-28 21 / 34