K007 Enroll-HD 2.0: updates to the Enroll-HD observational study

<h3>Background</h3> Enroll-HD was designed as an observational, longitudinal study to describe the natural history of Huntington’s disease (HD) and support further research. The study has generated a vast amount of data and bio-samples which have been used in multiple analyses that have facilitated understanding of HD progression and variability and aided in identification of novel drug targets. <h3>Aims</h3> The amendment to the Enroll-HD protocol (referred to as ‘Enroll-HD 2.0’) aims to update the study to better reflect current scientific needs and support the next generation of clinical trials and research. <h3>Methods</h3> The development of the amendment included a coordinating/writing team and multiple consultations with stakeholders. The final documentation (i.e., protocol, manuals, and sub-study protocols) are being professionally reviewed for consistency and clarity. <h3>Results</h3> The stated objectives remain unchanged. The amended protocol changes the study’s design to put greater focus on early HD and use the HD-ISS to guide recruitment. Key changes include: • Participants will be assigned to one of several cohorts, which allows for assessments and procedures to be tailored to disease stage. • Shift away from an unspecified broad recruitment approach towards targeting specific populations using the HD-ISS and aim for an overall size of ~25,000 active participants. • Flexibility to collect additional bio-samples. • Sub-studies (including imaging) will be available at some sites for some participants. <h3>Conclusions</h3> Updating Enroll-HD is essential in order to optimize the platform’s ability to support clinical research. The amended protocol will be distributed at Enroll-HD Congress 2024. Site start-up activities are scheduled to begin in 2025.