Pridopidine Phase 3 Study in Huntington's Disease

The goal of this clinical trial is to learn if pridopidine can slow the clinical decline of Huntington's Disease (HD) in adult participants. It will also inform about the safety of pridopidine. The main questions the study aims to answer are: Does pridopidine slow the overall worsening of HD over 1 year? Does pridopidine slow the worsening of specific aspects of HD over 1 year, namely the clinical progression, the ability to perform daily life activities (functional capacity), the mind's ability to process information (cognition), working of the muscles (motor function), and quality of life? Researchers will compare the drug pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works better than placebo to treat HD. During the first year of the study, participants will have the same chance to receive either pridopidine or placebo. Participants will: Take 1 pridopidine or placebo capsule twice daily for 12 months. Visit the clinic 6 times within 1 year for checkups and tests. All participants who complete this 1-year placebo-controlled study period will roll over into an additional 2-year study period during which all participants will receive pridopidine treatment, including participants who had received placebo during the first year. During this additional 2-year treatment period participants will visit the clinic a total of 6 times for checkups and tests.

Inclusion Criteria: * Adult-onset HD (onset of signs and symptoms and a clinical diagnosis at ≥21 years of age). * A diagnosis based on clinical features and the presence of ≥40 CAG repeats in the huntingtin (HTT) gene confirmed by historical laboratory quanitified results or by a diagnostic test at Screening. * Diagnostic confidence level (DCL) of 4 (DCL=4 unequivocal motor signs, ≥99% confidence) on the standardized motor exam Total Motor Score (TMS). * Total Functional Capacity (TFC) score of ≥7 at Screening and Baseline. * Cytosine-Adenine-Guanine (CAG)-Age Product (CAP)100 score ≥95 at Screening. * Independence Scale (IS) score ≤90% at Screening. * Total Motor Score (TMS) of ≥20 at Screening and Baseline. * Not using ADMs (VMAT2i and neuroleptics/antipsychotics) for at least 6 months prior to Screening visit. Importantly, it is not encouraged to discontinue the participants' ADM treatment solely for enrollment in the current trial. Exclusion Criteria: * Clinically significant cardiovascular disease (e.g. QTcF \>450 msec \[males\] or \>470 msec \[females\], arrhythmias, uncontrolled atrial fibrillation, or congenital long QT syndrome), seizure history ≤5 years, significant neurological disorders (e.g. intracranial pathology or cerebrovascular events), active/recent malignancy (unless localized and resolved), or any serious or uncontrolled systemic disease (e.g. hepatic, renal, respiratory, endocrine, infectious \[HBV, HCV, HIV\], or psychiatric) that may pose safety risk or interfere with participation. * Severe hepatic or renal impairment. * Any mutant huntingtin (mHTT) lowering therapy in the past year. * Medications that prolong QT interval, taken within 4 weeks of the baseline visit. * Use of pridopidine within 6 weeks or 5 half-lives before the screening visit. * Previous participation in intracranial gene therapy study. * Laboratory values that fall outside of the central laboratory's reference range at Screening and are considered clinically significantly abnormal by the Investigator and affect the participant's suitability to participate in the study or put the participant at risk if he/she enters the study in the Investigator's opinion. * Female participants who are pregnant, planning to become pregnant or breastfeeding.