• Number of sites and countries were updated to reflect the current trial status. • It was clarified that the local hematocrit value was to be used to determine CDAI score at Week 4 (Visit 4) so that clinical response could be determined immediately, the hematocrit value from the central laboratory assessment at Week 8 (Visit 6) was to be used to determine CDAI at Week 12 (Visit 8), and weight was to be measured at all visits where physical examination was not being performed, for use in CDAI determination. • Inclusion criterion 1c was amended to make the severity of disease, as defined by CDAI, consistent with endoscopic evaluation. Eligible patients had to have evidence of mucosal ulcers in at least 1 segment of the ileum or colon. • The term “initial isolate ileitis” was updated to “isolated ileal disease”. • Inclusion criterion 2 was amended to clarify that only infliximab was allowed as first-line anti-tumor necrosis factor (TNF) therapy; previous treatment with other anti-TNF therapies (specifically certolizumab) were not permitted. • The process to be used for primary analysis was clarified to state that efficacy data was to be included up to the Week 4 visit only and all available data for safety and other endpoints were to be included up to the data cut-off date. • Appendix 10.1 (Medication Blinding Procedure for Third Party Blinding) was updated to align the protocol with instructions included in the trial Pharmacy Manual.

•Trial methodology and related statistical method, and sample size calculations were updated to reflect an exploratory trial design. The design change allowed trial objectives to be achieved with a smaller number of evaluable subjects (65 in each group) and reduced total sample size of approximately 130 (from approximately 286). • Tuberculosis(TB) testing: Additional TB testing was included for Week 24 (Visit 14), before switching from Humira to BI 6995501, to clarify whether incidence of possible positive TB tests was linked to the comparator or test product. New text was included to clarify TB testing and subsequent follow up during the trial and exclusion criterion 8 was updated to emphasize that TNF inhibitor use was allowed. • Exclusion criterion 10 was updated to remove reference to positive anti-adalimumab antibodies at baseline to clarify that results of antidrug antibodies were not available at time of inclusion. • Description of CDAI assessment was amended to clarify the days patients were required to keep a symptom diary prior to each assessment. • Text was added to End of Treatment visit description to state that in event of early discontinuation, a patient was to receive treatment as deemed appropriate by the investigator and in accordance with applicable guidance. • Appendix 10.1 (Medication Blinding Procedure for Third Party Blinding) was updated to clarify how to handle used syringes in accordance with medical requirements and to align the protocol with instructions included in the trial Pharmacy Manual. • Additional table footnote was added to Appendix 10.2 (List of Laboratory Tests) to clarify that pathogens other than mandatory list may have been identified. • Due to trial design change, additional text was included in Appendix 10.3 (Details About the Statistical Considerations) to clarify that standard rules for noninferiority margin selection were not to be applied but, magnitude of preserved historical treatment effect was to be used.