A Phase I, 2-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-ascending Doses of Intrathecally Administered RG6496 in a Randomized, Placebo-controlled, Investigator/Participant-blind Study With an Open-label Extension in Huntington's Disease Gene Expansion Carriers
This is a first-in-human (FIH) study of RG6496 that will assess the safety and tolerability of single-ascending doses of RG6496 administered to huntington's disease gene expansion carriers (HDGECs). The study consists of two parts: Part 1 \[single-ascending dose\] followed by Part 2 \[open-label extension (OLE)\].
⁃ Part 1
• Confirmation of HDGEC status with cytosine-adenine-guanine (CAG) expansion \> 39.
• Confirmation of SNP carrier status of the target SNP
• Independence Scale (IS) score of ≥70, total functional capacity (TFC) ≥10, total motor score (TMS) \>6.
• Ability to read the words red, blue, and green and be fluent in the language of the informed consent form (ICF) and the tests used at the study site.
• Ability to walk unassisted.
• Total body weight \> 40 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per square meter (kg/m\^2) (inclusive) at baseline.
• Ability to undergo and tolerate MRI scans.
⁃ Part 2
• Completed the post-dose safety follow-up period in the Part 1 of the study.
• In the opinion of the Investigator, the participant has not experienced a worsening in health that precludes their safe continued participation in the study.