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 (HD).

Inclusion Criteria: DB Period: * HD gene expansion mutation carrier status with a cytosine-adenine-guanine-age product (CAP) score of 400-500 inclusive * Either: * Prodromal HD (defined as Diagnostic Confidence Level (DCL) 2 to 3, Independence Scale (IS) ≥70, and TFC ≥8); Or * Early manifest HD (defined as DCL 4, IS ≥70, and TFC ≥8) * Total body weight \> 40 kilograms (kg) and a body mass index (BMI) within the range of 18-32 kilograms per meter square (kg/m\^2) * Study companion OLE Period: * Participants must have completed the DB treatment period * Participants must remain in the DB Safety follow-up period until OLE period starts Exclusion Criteria: DB Period: * Current or previous use of an antisense oligonucleotide (ASO) (including small interfering ribonucleic acid \[RNA\]) 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 milligrams per day \[mg/day\]), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin * History of gene therapy, cell transplantation, or brain surgery * Hydrocephalus * Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug * History 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 OLE Period: * Early discontinuation from the DB treatment and the safety follow-up (SFU) periods * Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required * Current or previous use of an ASO other than tominersen (including small interfering RNA) or any other HTT-lowering therapy * Hydrocephalus * Received any active investigational treatment other than tominersen during or since completion of the DB treatment period Key inclusions/exclusion criteria are listed here. Other protocol-defined I/E criteria may apply.