The following main changes were implemented: - Addition of safety as a trial objective and of TEAEs as secondary endpoint, as safety is a central component of Phase IIa studies. - Change of time point for UC diagnosis to ≥5 months prior to screening in the inclusion criteria to allow stable TNFi treatment for ≥4 months prior to randomization.

The following main changes were implemented: - Deletion of the lower body weight limit of 60 kg in Inclusion Criterion 2 and corresponding update of the section on dose selection, as a lower weight limit was no longer considered to be needed. - Modification of in Inclusion Criterion 4 to clarify that ‘unchanged dose’ includes unchanged dose and dosing interval.

The following main changes were implemented: - Increase of the upper age limit in Inclusion Criterion 1 from 60 to 75 years to facilitate recruitment. - Increase of the upper body weight limit in Inclusion Criterion 2 from 100 to 120 kg to facilitate recruitment; corresponding update of the benefit-risk assessment to justify that this is not expected to affect PK of the trial drug. - Modification of Inclusion Criterion 4 to facilitate recruitment by adding the possibility of TNFi treatment with adalimumab and golimumab with unchanged doses for ≥2 months and specification that patients may or may not have received up to 2 different prior TNFi treatments; corresponding modification of the benefit-risk assessment and discussion of trial design. - Modification of Exclusion Criterion 3 to state that prior use of more than 2 different TNFis was not allowed, to facilitate recruitment. - Change of the timing of the primary endpoint from Week 8 to Week 12, and corresponding update of the wording for the primary objective and all other affected sections. Week 12 was defined as a project standard time point for primary efficacy measurement as initial data indicated a potential for slower onset of action for the spesolimab mechanism of action: The primary endpoint was changed to ‘mucosal healing (MCS mESS ≤1) at Week 12’ instead of ‘at Week 8’; The secondary endpoint ‘mucosal healing (MCS mESS ≤1) at Week 12’ was deleted; A further endpoint ‘mucosal healing (MCS mESS ≤1) at Week 8’ was added. - Deletion of the following endpoints at Week 8 from the list of secondary endpoints and moving of these endpoints to the list of further endpoints: ‘Modified clinical remission based on MCS (total modified MCS ≤2 and: RBS =0, Stool Frequency Score =0 or 1 and drop ≥1 from baseline, AND mESS ≤1) at Week 8’; ‘Clinical remission based on MCS (total MCS ≤2 points, and all subscores ≤1 point) at Week 8’; ‘Histological remission (RHI score ≤6) at Week 8’.