Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease

Key Inclusion Criteria: * Diagnosed with early manifest Huntington's disease * Male or female, aged 25 to 65 years, inclusive, at the time of informed consent * Able and willing to meet all study requirements, including travel to Study Center and participation in all procedures and measurements at study visits * Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the participant to select trial visits and to be available to the Study Center by phone if needed * Able to tolerate MRI scans, blood draws and lumbar punctures * Reside within 4 hours travel of the Study Center Key Exclusion Criteria: * Clinically significant medical condition, such as severe chorea, active suicidal ideation or any other conditions which would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study * Recent treatment with another investigational drug, biological agent, or device * Prior treatment with an antisense oligonucleotide \[including small interfering ribonucleic acid (siRNA)\] * Any history of gene therapy or cell transplantation or any other experimental brain surgery * Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter * History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch * Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated * Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study