Version 2.0: -The planned number of sites was increased from approximately 50 to approximately 75 sites which could include other regions apart of Europe. -A new exclusion criterion (Exclusion Criterion 31) was added to exclude participants who have received a COVID-19 vaccine within 4 weeks before randomization or if COVID-19 vaccination was ongoing at the time of screening. -Assessment of PD biomarkers at Week 4 and Week 8 was added to elucidate early responses and their maintenance up to the first 3 months after initiation of dosing. - The coagulation panel was removed from the laboratory safety endpoints.

Version 5: -AUEC(0-W26) of serum CTX was added as a co-primary endpoint for registration purposes in the EU and the EEA only, following EMA recommendation. This approach implied a change in the definition of the study objectives, where PD was no longer defined as a key secondary objective, and was instead considered a secondary objective, or a co-primary objective for the EMA submission (while remaining a secondary objective for FDA). Percent change in serum CTX was then regarded as a secondary endpoint for both agencies. -Exclusion Criterion #16, referring to the eligibility of patients with medical conditions that could have interfered with the study conduct, interpretation of study data, and/or otherwise could have put the participant at an unacceptable risk, was updated to clarify that participants with rheumatoid arthritis or other medically relevant autoimmune conditions were not eligible for the study. This exclusion was due to the potential risk of exacerbation of preexisting conditions during the long study duration (78 weeks). In addition, the potential usage of protocol prohibited medication in case of a flare could have resulted in protocol deviation and lower compliance. -Footnotes in the Schedules of Assessments were moved and reworded to clarify when a predose sampling was required. -A ±7-day window was added for the DXA scan to be performed at Week 52 (Day 365) and Week 78 (Day 547). -Wording was added to clarify that: ▪ when 2 blood samples were required, the second sample did not need to be in a fasting state; ▪ if the site was asked to re-acquire a DXA scan after analysis by the central imaging vendor, this was also in duplicate; ▪ suitable ancillary care in accordance with local practices was provided to patients with unresolved AE, unless the participants was lost to follow-up: ▪ continuous AEs had to be reported as a single AE with severity changes: the highest severity was to be chosen to document the single AE at the end.

Version 6.0: -A Coordinating Investigator was included in the protocol. -One of the changes included in the previous Protocol Amendment 4, to clarify the requirement for fasting state, had not been correctly implemented for the Week 52 samples, and was corrected in the current protocol amendment. -Similarly, one of the changes included in the previous Protocol Amendment 4, allowing the DXA to be performed within ±7 days of the Week 52 and Week 78 study visits, was not stated in all relevant sections of the protocol and this was corrected in the current protocol amendment.