GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease.

This study will evaluate the safety, biomarkers, and efficacy of tominersen compared with placebo in participants with prodromal and early manifest Huntington's Disease.

Key Inclusion CriteriaSigned study companion consent form. A study companion is required for all participants.HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows:Age x (CAG repeat length -33.66)-Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3)Companion Inclusion Criteria- HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows: Age x (CAG repeat length -33.66)Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3)Signed study companion consent form. A study companion is required for all participants.Key Exclusion CriteriaCurrent or previous use of an ASO (including small interfering RNA) or any HTT lowering therapy (including tominersen)Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless </= 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparinHistory of gene therapy, cell transplantation, or brain surgeryHydrocephalusPregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drugHistory of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening