Global amendment 2 was implemented after approval by the competent authority and IEC or IRB. The following main changes to the CTP were introduced by this amendment a:ddition of the further endpoints “proportion of patients with Complete Remission at Week 12” and “proportion of patients with Endoscopic Remission at Week 12”; inclusion criterion #3 was updated with regard to the definition of moderate to severe activity; inclusion criterion #5 was updated to add the requirement of documentation for past inadequate response or loss of response; inclusion criterion #6 and the restrictions were updated to allow the use of prednisone or equivalent and of oral beclomethasone dipropionate for the treatment of UC as well as the short-term use of systemic corticosteroids for the treatment of AEs; inclusion criterion #8 and the restrictions for women of childbearing potential and male participants were updated to align with updated contraception requirements in the Investigator’s Brochure (IB); exclusion criterion #9 was updated with regard to the required time window of faecal transplant; exclusion criterion #12 was updated with regard to active tuberculosis and the details for the required TB testing; in the study definitions, surgical procedure was added to the rescue treatments; some of the exclusion criteria were aligned with project definitions and the IB update; cytokine release syndrome was deleted from the list of AESIs.

This amendment was necessary to implement changes (some of which were requested by Health Authorities) prior to the initial approval and start of the trial. The following main changes to the CTP were introduced by this amendment: The definition of hepatic injury was changed following a request from the FDA; a stopping rule related to a hepatic injury alert without identification of an alternative cause was added; in exclusion criterion #16 relating to pathological safety lab parameters, the threshold for the minimal haemoglobin level was increased based on FDA recommendation; exemptions from the SAE reporting were removed.

The following main changes to the CTP were introduced by this amendment: the option to measure drug levels of previous biologics to shorten the washout period to less than 8 weeks was introduced; restrictions regarding previous and concomitant treatment were updated; exclusion criterion #14 was updated with regard to the required time window for remote history of malignancy; exclusion criterion #5 was updated to further specify that the positive stool examination for Clostridium difficile corresponded to a positive toxin A/B test. Investigators and other site personnel were informed upfront (dated 29 Apr 2019); the AESI “Infusion reactions including anaphylactic reaction” was renamed to “Systemic hypersensitivity including infusion reaction and anaphylactic reaction” to align the terminology with project standards; the AE collection definition was updated for patients rolling over into the open-label extension trial to ensure that any AE reported prior to the first dosing in the extension trial was assigned to trial 1368-0005; in the case of rescheduled visits, the calculation of subsequent visits was changed from the date of the previous visit to Day 0; it was clarified that the recommendation to perform a PPD skin test in the case of undetermined re-test results of the QuantiFERON®-TB test applied for Screening and the EOS Visit; because of premature termination of recruitment, none of the patients was randomised after Global amendment 3 had been implemented.