In Protocol Version 2.0, study personnel information was corrected and/or updated; background information was modified to include new reproductive toxicity findings (the discussion of contraceptive measures was also updated accordingly) and clinical pharmacokinetic and safety data; inclusion and exclusion criteria were modified; and clarifications and/or modifications to efficacy, safety, and other assessments and procedural activities were incorporated. Additional administrative and/or editorial revisions were incorporated to eliminate discrepancies or provide clarification.

In Protocol Version 3.0, the treatment duration was extended from 12 months to 15 months in order to allow for greater placebo decline; as a result, an additional post-baseline on-treatment visit and an additional telephone contact for assessment of safety were added and incorporated throughout the study protocol. Given that all subjects received some amount of LMTM, the Sponsor did not plan to routinely unblind treatment allocation for suspected, unexpected serious adverse reactions (SUSARs) for expedited reporting; guidance for Sponsor reporting of SUSARs to regulatory authorities was revised accordingly. Revisions also included modifications or clarifications to background information; inclusion and exclusion criteria; study drug administration and packaging; efficacy, safety, and other assessments/procedures; statistical analyses; and administrative procedures. Additional editorial revisions were incorporated to eliminate discrepancies or provide clarification.

In Protocol Version 6.0, modifications (relative to Protocol Version 3.0) included updates to administrative and background information, clarifications to exclusion criteria, modifications to study objectives and efficacy/statistical analyses, safety and exploratory assessments and/or procedures (including for quality assurance and clinical monitoring), as well as other minor revisions to provide further clarification. It should be noted that the protocol was amended in the interim to modify the procedure for dose reduction and to no longer require magnetic resonance imaging (MRI) monitoring for evaluation of amyloid-related imaging abnormalities; however, as these interim amendments were not distributed for implementation at the clinical sites and were superseded by Protocol Version 6.0, the dose reduction procedures and MRI monitoring were maintained.