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

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Protocol Version 3 14/01/2013 After 30mins (if tolerated) 300mg/hour 180mls/hour After 30mins (if tolerated) 350mg/hour 210mls/hour After 30mins (if tolerated) 400mg/hour 240mls/hour 4.5.2 Tocilizumab Preparation will be performed by a suitably trained member of the study team as per local policy Instructions for Dilution and Suitable Diluent: · The volume of Tocilizumab concentrate required for the patients dose should be calculated. · Using aseptic technique the required volume of sodium chloride 0.9% should be removed from a 100ml infusion bag. · The required volume of Tocilizumab should be withdrawn from the vial and placed in the 100ml infusion bag to give a final volume of 100ml · To mix the solution, gently invert the infusion bag to avoid foaming. Do not shake. Method and Rate of Administration: IV infusion: The final 100ml infusion bag should be administered by IV infusion over a one hour period 1 . Using IV Volumat Pump: The pump does not have a preset setting for Tocilizumab. Using Injectomat Syringe driver: The syringe driver does not have a preset setting for Tocilizumab. Example Calculation: (Adult Patients) For a 70kg, the dose is usually 560mg every 4 weeks (70kg x 8mg/kg). This dose requires 28ml of Tocilizumab concentrate – ie 20ml from a 1 x 400mg vial and 2 x 4ml (2 x 80mg) doses. Twenty eight ml is withdrawn form the 100ml infusion bag and the 28ml form the vials added to the infusion bag. The resulting solution is then given as an IV infusion over a one hour period. Flushes Compatible: Sodium Chloride 0.9% 1 Adverse effects which may be caused by IV administration and suggested monitoring: · Common side effects include abdominal pain, mouth ulceration, gastritis, raised hepatic transaminases, dizziness, peripheral oedema, hypertension, hypercholesterolaemia, headache and infection. Special Handling Precautions: The reconstituted solution should be used immediately due to sterile concentrate not containing any preservatives. The Tocilizumab will be administered at room temperature by controlled infusion into an arm vein over a one hour period. In exceptional cases this time may be extended to up to 6 hours. The infusion speed must be 10 mL/hour for 15 minutes and then increased to 130 mL/h to complete the dosing over 1 hour. The entire 100 mL content of the infusion bag must be administered. 20 mL of normal saline will be administered following the infusion of study medication to flush the remaining study medication through the intravenous set. 4.2 Accountability/Receipt /Storage and Handling of IMP The investigator is responsible for the control of drugs under investigation. Adequate records for the receipt (e.g. Drug Receipt Record) and disposition (e.g. Drug Dispensing Study: R4RA EudraCT: 2012-002535-28 20 / 34
Protocol Version 3 14/01/2013 Log) of the study drug must be maintained. Accountability will be assessed by maintaining adequate drug dispensing and return records. This will be delegated to the local site pharmacy. The IMP will be stored by the local pharmacy. Accurate records must be kept for each study drug provided. These records must contain the following: • Documentation of drug shipments received from the sponsor (date received and quantity) • Disposition of unused study drug not dispensed to patient When the study is completed, the investigator will return all completed Drug Dispensing Logs to the trial co-ordinator. Also, any unused study drug and Drug Return Records should be returned to the Monitor. The investigator's copy of the Drug Return Record(s) must accurately document the return of all study drug supplied. 4.3 Dispensing of IMP A Drug Dispensing Log will be kept current and will contain the following information: • the identification of the patient to whom the study medication was dispensed • the date[s], quantity of the study medication dispensed to the patient • the date[s] and quantity of the study medication returned by the patient. All records and drug supplies must be available for inspection by the Monitor at every monitoring visit. When the study is completed, the investigator will return all completed Drug Dispensing Logs to the monitors. 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. Study: R4RA EudraCT: 2012-002535-28 21 / 34
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Protocol Title : A Randomised, open
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Protocol Title : A Randomised, open labelled study in anti ... - EME

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