A Randomized Study of SPK-10001 Gene Therapy in Participants with Huntington's Disease

Key Inclusion Criteria:

• Have confirmed huntingtin (HTT) cytosine-adenine-guanine (CAG) repeat length ≥40 ongenetic testing and confirmation diagnostic test by the central laboratory (CL) atscreening.

• Have striatal atrophy demonstrated by caudate/intracranial volume less than theage-adjusted cutoff values associated with HDISS Stage 1.

• Have UHDRS Total Motor Score (TMS) equal to or greater than the age-adjusted cutoffvalue associated with HDISS Stage 2.

• Have UHDRS Total Functional Capacity (TFC) greater than or equal to 11.

• Use of cholinesterase inhibitors, memantine, amantadine, or riluzole must have beenat stable dosing for at least 12 weeks before screening and baseline and anticipatedto remain stable during the first 12 months after SPK-10001 administration.

• Antidepressant or benzodiazepine use must have been at stable dosing for at least 12weeks before screening and baseline and anticipated to remain stable during thefirst 12 months after SPK-10001 administration.

• Antipsychotics for motor symptoms or mood stabilization (i.e., irritability oraggressive behavior) and/or tetrabenazine, valbenazine, or deutetrabenazine musthave been at a stable dose for at least 12 weeks before screening and baseline andare anticipated to remain stable during the first 12 months after SPK-10001administration.

Key Exclusion Criteria:

• A safe trajectory is not able to be identified for targeting placement of thecannula into the caudate or putamen on both sides of the brain due to extent ofatrophy or other anatomical features.

• Have received an antisense oligonucleotide therapy during the past year.

• History of deep brain stimulation.

• History of or intention to undergo gene therapy, cell transplantation, or brainsurgery during the course of the study.

• Have participated in an investigational drug study with a systemic administrationwithin 6 weeks or 5 half-lives of screening, whichever is longer.

Additional protocol-defined inclusion/exclusion criteria apply.