• Clarity added to protocol around procedures relating to mechanistic studies • Corrections/typos where required • Increased window for some screening investigations prior to randomisation, and timing of CDAI in relation to colonoscopy • Inclusion of the use of the IBD BioResource to identify potential participants • Addition of HBI between mobilisation and conditioning, CDAI and HBI at both screening and baseline, added stoma version of IBDQ for participants where this is required • Updates to PIS on advice from TSC – timing of discussion with both specialties, noted that most common side effects likely to occur in almost all patients • Submitted reformatted versions of the validated participant questionnaires • Minor updates to formatting for healthcare resource use questionnaire, symptom diary and vaccination proforma

• Changes to PI at Edinburgh and Nottingham sites • Secondary outcome added in relation to MRI and MaRIA score • Additional mechanistic serum sample added at week 40 visit • Addition of potential storage of stem cell samples for use in future research • Added Karnofsky performance status at screening and week 48 for all participants • Information added in relation to press release to aid recruitment, and potential use of a study Twitter account • Participant allocation letter submitted which can be used to follow up informing participants of their allocation where face to face is not possible • Addition of a vaccination advice sheet for GPs

• To allow the use of PICs, and to add Nottingham NHS Treatment Centre as a PIC for the Nottingham site

• The removal of details of MA holder for each IMP in section D2-1 of the application. The intention has always been for sites to use any brand of the IMPs in this study, and whilst the correct section of the application was completed to reflect this, details from the sample SmPCs submitted originally was also included, which implied that those brands were specified.

• To add King’s College Hospital London as a non-recruiting site, and to change the site type for Guy’s & St Thomas’ to a non-treatment site.

• Administrative changes to the protocol to update the organisations for two collaborators, Sponsor contact email address, CI deputy details • Increase the window for screening investigations from within 4 weeks to 8 weeks of randomisation • Provided clarity on how the primary outcome will be assessed for patients who have had ileo and/or colonic resection, but are still eligible to take part in the trial • Correction to DMEC meeting frequency in line with the DMEC Charter • Correction to treatment section in the PIS to note that mobilisation cyclophosphamide will be given on one day, rather than two. • Clarification in the PIS that endoscopy might be undertaken if the bowel cannot be examined using ileocolonoscopy. • The SmPC for filgrastim has been updated since the start of the study; the revised version has been submitted with this amendment to update the RSI. • The SmPC for cyclophosphamide has been updated since the start of the study; although there have been no changes to the safety aspects, the updated version has been included with this amendment so that sites can have access to the latest information relating to the IMP.

• Addition of genetic and or functional tests during screening to exclude monogenic cause of intestinal inflammation in patients with predictive clinical phenotype • To allow possibility of second attempt at mobilisation with reduced or no cyclophosphamide in patients who fail to mobilise first time • Admin changes and updates to protocol • Clarified definition of SES-CD ulcer size subscore for eligibility and outcomes • Updates to PIS for GDPR requirements, and genetic testing as above • Additional two flowcharts to help explain trial to participants

Increase in dose of methylprednisolone (NIMP) from 1mg/kg/day to 2mg/kg/day, with scope to increase further up to 500-1000mg in the setting of an ATG reaction. Amendment in response to Urgent Safety Measure (July 2019).

Administrative changes to reflect change in trial manager and research assistant. Removal of the circle Nottingham as this is now part of Nottingham University Hospitals NHS Trust. Allow the use of an alternative to MRI such as a CT scan for screening if patients are unable to have an MRI. Addition that MRI will not be carried out at week 4, week 24 or week 48 if this is contraindicated. At week 24 an assessment of whether anti-TNF therapy is indicated will be based on endoscopic evidence and if needed, abdominal ultrasound. Addition that any laboratory test result which is out of range, and clinically significant, will be recorded as an adverse event, unless it is expected as part of the patient’s disease presentation, or reflects the status of their baseline disease. Consideration about reintroducing anti-TNF at week 24 for patients with multiple sclerosis. Anti-TNF therapy may not be appropriate for these patients therefore it will be reviewed on a case by case basis and discussed at MDT. Suitable alternative such as vedolizumab may be offered. Changes to the SmPC for filgrastim and thymoglobulin.

Temporary Halt following fatal SUSAR

Addition of letter to update patients on the closure to the ASTIClite trial.