RITAZAREM CRF Completion Guidelines

RITAZAREM CRF Completion Guidelines 10 Sept 2013 Version 1.2 Author: Michelle Lewin RITAZAREM Trial Coordinator Michelle.lewin@addenbrookes.nhs.uk Tel: +44(0) 1223 349350 Fax: +44(0) 1223 586767 Version Date Changes 1.0 3 June 2013 1.1 12 July 2013 Renaming of Infections (non- SAE) Form to Infections Form 1.2 10 September 2013 PROMIS questionnaire used from Month 0 onwards, not from Screening RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 1 of 6

General Instructions Abbreviations: Case Report Form Completion Guidelines AE BSA BVAS/WG CDA CRF CCTU EQ5D FDA GCP IV NA NAD ND NK PGA PROMIS SAE SF-36 SUSAR adverse event body surface area Birmingham Vasculitis Activity Score for WG Combined damage assessment index case report form Cambridge Clinical Trials Unit EuroQol 5D Quality of Life Questionnaire Food and Drug Administration Good Clinical Practice Intravenous not applicable no abnormalities detected not done not known Physicians Global Assessment Patient Reported Outcomes Measurement Information System serious adverse event Short Form (36) Health Survey Suspected Unexpected Serious Adverse Reaction General guidance Always refer to the study protocol before completing forms. Please ensure that you are using the most-to-date version of the CRF. A comprehensive list can be found on the RITAZAREM trial website at: www.rarediseasesnetwork.org/vcrc/ritazarem All text must be provided in English. CRFs should always be signed and dated by the person completing them, and that person should be listed on the RITAZAREM delegation of responsibilities log (located in the site file) as being authorised to complete CRFs. By signing the CRF you are confirming that the information is correct to the best of your knowledge. Ensure data entries are consistent with the source data (usually the patient s medical notes). All data recorded on the study forms will be verifiable in the source documents maintained by the clinical sites according to FDA and ICH Good Clinical Practice (GCP) guidelines. Once a CRF is completed, please ensure a copy is placed in the patient s trial file. This may be a photocopy or the original if the CRFs are faxed/scanned and emailed to the coordinating data centre. Completed CRFs should be returned to the coordinating office in Cambridge within 2 weeks of completion. If it becomes apparent that an error has been made on the CRF, please send an amended copy to the CCTU with a cover note to highlight that this is an updated version from the one previously sent. Ensure a copy of the amended CRF is retained at site along with the copy of the original which was sent. If a patient fails to attend an appointment or if for some other reason a scheduled assessment is missed the CCTU must be informed so that we can make a note of this on our database. Always use black pen. Always write clearly ensuring that the entries are legible to others. RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 2 of 6

Avoid abbreviations and acronyms, unless they are standard medical abbreviations or known to be acceptable. Ensure that you complete the header information on each page consistently. Always fill in EVERY field on each CRF page (unless indicated otherwise). If a procedure was not done or not applicable, enter ND or NA where appropriate, or tick/check the not done box. Do not write outside of the designated boxes. Completely fill in each box using leading 0 if needed, e.g. To amend incorrect data on a CRF page: score through the error with a single line, write the correct data nearby, initial and date each correction, do not obscure the original entry (do not use correction fluid). Do not record incomplete dates (i.e. if you know the month and year, but not the day, record- NK/APR/05). Record dates in the requested format dd/mmm/yy (e.g. 13 MAY 12). Tick/check the box to indicate the units used for weight, height, lab results etc. If a medication was given for an infection or a serious adverse event, make sure it is documented as fully as possible. Some questions will require a code to be entered according to a key provided (e.g. the Concomitant Medications form). Please ensure that you read the key for each section and follow any further instructions provided. Some CRF pages, for example the Concomitant Medications form and the Infections form, may require more than one page to be completed, but the number of pages is unknown before CRF completion. In this case, digit boxes are provided in the notation page of, which should be completed to indicate how many pages were filled populated. Questionnaires (SF-36, EQ-5D, PROMIS) are completed by the study participant. Local language versions of the questionnaires are available. The only adverse events being collected for RITAZAREM are infections requiring treatment with intravenous (IV) or oral antimicrobial, antiviral or antifungal medication, or infections commonly understood as opportunistic. There is no general AE reporting form, only an Infection Form. There will be a copy of the SAE reporting form on the website, and the form includes a front sheet detailing completion instructions and reporting timeframes as well as definitions of SAEs. RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 3 of 6

CRF Title Eligibility Form Enrolment Form Baseline Medical History Form When CRFs need to be completed At screening, once the patient has given informed consent, before enrolment At screening, once the patient has given informed consent At screening, once the patient has given informed consent and has been deemed eligible for the study Check List Form At each visit (Screen, Month 0, 1.5, 3, 4, 8, 12, 16, 20, 24, 27, 30, 36, 42 and 48) Clinical Laboratory Tests Form At each visit (Screen, Month 0, 1.5, 3, 4, 8, 12, 16, 20, 24, 27, 30, 36, 42 and 48) Follow-Up Form At each visit after Month 0 BVAS/WG Form At visit Months 0, 1.5, 3, 4, 8, 12, 16, 20, 24, 27, 30, 36, 42 and 48 CDA Form At visit Month 0, 4, 12, 24, 36, and 48 EQ5D Form At visit Month 0, 4, 12, 24, 36, 42, and 48 SF-36 Form At visit Month 0, 4, 12, 24, 36, 42, and 48 PROMIS At every visit from month 0 to month 48 Concomitant Medications Form New form at each visit Randomisation Form At Randomisation (Month 4 ± 14 days) Treatment Form - Rituximab Week 1, 2, 3, 4 (Induction Phase); then, if patient randomised to rituximab arm, Months 4, 8, 12, 16 and 20 (Maintenance Phase). If a patient relapses and is treated for the relapse Relapse Form As needed Infections Form Each time a patient is diagnosed with an infection (infection is any episode requiring antimicrobial, antiviral or antifungal medication), and each time there is updated information on an infection, until the infection has resolved. To be reported within 15 days of the event. SAE Form Within 24 hours of becoming aware of an SAE/SUSAR (see SAE coversheet for details). Check the event for seriousness; if the event meets 1 of the 5 serious criteria listed on the SAE Form, determine the causality and expectedness then fill in the SAE form concluding the nature of the event and subsequent actions. Pregnancy Form When a patient on the study falls pregnant while on study medication, and when there is a pregnancy outcome** Withdrawal Form If a patient withdraws/is withdrawn from the trial End of Trial Form When a patient reaches the end of the trial* Death Form When a patient dies *common close-out will be when the last patient reaches 12 months follow up (36 months after entry into the trial). **the patient must have given consent for follow-up of the pregnancy outcome RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 4 of 6

Page Specific Instructions Header information- all pages Field Comments Consistency check Study ID 6 digit: first three are the site ID*, Correct format second three are patient study ID. For example, the first patient in Boston, USA will be US1-001 Participant Initials If 2 initials, use dash in the middle digit box Not blank, check consistency Date of Birth Use format dd/mmm/yy Not blank, check consistency Evaluation Date Use format dd/mmm/yy Not blank, check consistency *Site ID will be provided by the CCTU. BVAS/WG There is a separate BVAS/WG form for each assessment point; please ensure you use the correct form for the assessment. BVAS/WG is designed to capture clinical features that are directly due to active disease. In addition, the instrument separates the features that represent new or worse disease activity from those that represent persistent activity. Only tick the Persistent box only if the abnormality is persistent disease activity since the last assessment and not worse within the previous 28 days. Only tick the New/Worse box tick box if the abnormality since the last assessment is newly present or worse within the previous 28 days. When scoring BVAS/WG, it is important not to confuse activity with damage. Damage, defined as the presence of non-healing scars, is a concept distinct from current disease activity. Please remember to complete the Physician s Global Assessment (PGA) at the end of the BVAS/WG form. Clinical Laboratory Form Laboratory test results are permitted to be within ± 2 weeks of the date of the study evaluation. Concomitant Medications Please note, the Concomitant Medications form is not a running log. A new form must be completed at each assessment point, even if there are no changes to concomitant medications. All on-going concomitant medications must be documented on a new CRF page at each assessment. Please record only prescribed medications; it is not necessary to list vitamins and other dietary supplements. If more than one page is needed at a study evaluation, please complete multiple pages and populate the page number at the footer of the form. Eligibility Review Form All questions must be answered on the eligibility review. For a patient to be eligible, all inclusion criteria questions must be answered yes and all the exclusion criteria questions must be answered no. End of Trial Form The End of Trial is when a patient has completed 24 months follow-up (on study for 48 months), or when the last patient reaches 12 months follow-up (36 months after entry into the trial) and common close-out occurs. All patients must have this form completed unless they die during the trial period or if they withdraw consent. Enrolment Form RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 5 of 6

Enter the patient s height, weight, predniso(lo)ne regimen, ANCA and relapse type on the form. Log into the enrolment/randomisation system at https://prod.tenalea.net/cctu/dm/default.aspx and enter the required information. The system will calculate and output the Body Surface Area (BSA) and the induction dose of rituximab (mg/infusion), and provide the target randomisation date. The study ID of the patient will also be generated at this stage. Enter these data on the enrolment CRF. Infection Form A new infection form must be completed for every infection, even if concurrent with another infection. If more than one page is needed at a study evaluation, please complete multiple pages and populate the page number at the footer of the form. If an infection is on-going, please leave the date of resolution blank. When new information on an infection is available (or if the infection resolves), please submit a new form containing the new information, ticking the box to indicate this is further information on a previously-reported event. Please do not update an original, previously submitted CRF page. If the infection meets any of the definitions of an SAE, i.e. results in death, is life-threatening, requires hospitalisation or prolongs hospitalisation, results in persistent disability or incapacity, or consists of a congenital anomaly or birth defect, then an SAE form must be completed in addition to the infection form. Please note:saes must be reported within 24 hours of becoming aware of the event. Randomisation Form This should be completed at Month 4 ± 14 days. Enter the patients current predniso(lo)ne dose and BVAS/WG score. Log into the randomisation system at https://prod.tenalea.net/cctu/dm/default.aspx, and enter the required information. The system will provide the treatment assignment. Enter these data on the randomisation CRF. Relapse Form The date of relapse for the purpose of this study is the date that symptoms necessitated a treatment change. This does not have to be the evaluation date on the relapse form, as relapse can occur between study visits. Please provide an answer to all the questions, even if you have answered yes to major relapse. Relapsed patients (first major or second minor relapse) leave protocolised treatment but remain on protocol for follow-up, i.e. they continue to follow the schedule of assessments for follow-up purposes. Serious Adverse Event (SAE) Form Please refer to the cover sheet of the SAE form for definitions, reporting timelines and where to send SAE forms. The trial details of study title, R&D number and EudraCT number will all be pre-populated on the form. You should complete the patient s initials, date of birth and subject ID. Please indicate if this is an initial or follow up report, and complete your centre number (the first three digits of the subject ID), as well as the remaining details. Treatment Form The treatment form should be used to record all the details concerning rituximab infusions, for both the induction and maintenance phases. Please complete a new form each time an infusion is given. The infusion number should be circled on the form. Any deviations from the infusion protocol should be detailed on the form. Withdrawal Form For the purposes of this study, withdrawal is withdrawal of protocolised treatment and not withdrawal of protocolised follow-up. All patients must continue to be followed up for safety purposes unless consent has been withdrawn. RITAZAREM CRF Completion Guide, v1.2, dated 10_September_2013 Page 6 of 6