Amendment 1: The eligibility criteria were changed from 1 prior therapy to 2 prior therapies. The eligibility criteria were updated to specify highly effective methods of contraception per Clinical Trials Facilitation and Coordination Group recommendations (part of the Heads of Medicines Agencies). The conditions for (temporarily) withholding treatment, early discontinuation from the study, and early discontinuation from treatment were updated. The determination of the sample size, the primary endpoint analysis, and the key secondary endpoint analysis subject to alpha control were updated. A key secondary efficacy endpoint subject to alpha control was added. Japan-specific eligibility criteria were removed in lieu of a separate Japan-specific protocol.

Amendment 2: The protocol was aligned with ICH E2A guideline and the categories of seriousness on the sponsor’s SAE report form.

Amendment 3: The postbaseline platelet count measurement was permitted within 1 day of the next procedure, for more flexibility. Fostamatinib was added as a permitted concurrent ITP medication upon its regulatory approval as ITP therapy. Eltrombopag was replaced with “oral thrombopoietin receptor agonist (TPO-RA)” to consider all TPO-RAs. An eligibility criterion was added regarding live/live-attenuated vaccines, as a preventive protection measure for participants. The key secondary endpoint analysis subject to alpha control and the determinations of sample size were updated to allow data from participants who met the definition of disease control during the study but who subsequently did not meet the criteria for disease control before the end of the treatment period, to contribute more data to the final estimate of the length of disease control. Derivation of pharmacokinetic parameters by noncompartmental methods became less appropriate with the limited pharmacokinetic sampling. Therefore, only efgartigimod serum concentration data were summarized. It was added to specify that IgG testing could not be performed locally to avoid unintentional unblinding. COVID-19 mitigation measures were added.

Amendment 4: The eligibility criterion regarding the number of platelet counts at study entry was updated to allow more flexibility. Acceptable methods of contraception were added to the eligibility criteria per the results of the reproductive toxicity studies. The visit duration after the end of IMP infusions was shortened based on supporting safety data. The definition of AEs was updated and clarified. The definition of rescue therapy was updated to consist of an “occurrence,” which was defined as a ≤5-day period in which 1 or more rescue treatments were administered to a participant.

Amendment 5: The primary endpoint analysis was updated. The key secondary endpoint analysis subject to alpha control was updated for consistency with the primary endpoint analysis.

Country-Specific Amendment France version 5.1: The description of the 24-week treatment period (ie, “trial period”) was updated to “treatment period” to clarify the duration of the period, per central IEC request. Clarifications in the protocol summary were added to state the number of visits and the time duration of each visit. Reference to the Summary of Product Characteristics was added to the Concurrent ITP Therapy section. The participant demographic assessment was modified to provide that source data verification of race and ethnicity should not be performed per French regulations.

Country-Specific Amendment Japan version 5.1: The sample size for Japanese participants was added. The stratification and randomization strategy was updated for Japanese participants. Specific safety measures were added. The eligibility criteria were aligned with Japanese regulations: the minimum age of enrollment was changed to 20 years of age to align with Japanese age of majority, a definition of a Japanese participant was added, and a Helicobacter pylori test was added per current management of ITP in Japan.