The primary objective of this study is to assess the efficacy of laquinimod as treatment in participants with HD after 52 weeks using the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS or TMS).

Inclusion Criteria:

• Documentation of prior positive genetic testing for HD, or a clinical diagnosis of symptomatic HD.

• Presence of 36-49 cytosine-adenosine-guanine (CAG) repeats, inclusive, in the huntingtin gene based on centralized CAG testing during screening.

• Male or female between 21-55 years of age, inclusive, with an onset of HD at or after 18 years of age.

• Women of child-bearing potential (women who are not post menopausal or who have undergone surgical sterilization) must practice an acceptable method of birth control for 30 days before taking the study treatment, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment was administered.

• A sum of greater than (>) 5 points on the UHDRS-TMS at the screening visit.

• Able and willing to provide written informed consent prior to any study related procedure being performed at the screening visit. Participants with a legal guardian should be consented according to local requirements.

• Willing to provide a blood sample for genomic CAG analysis at the screening visit.

• Willing and able to take oral medication and able to comply with the study specific procedures.

• Ambulatory, being able to travel to the study center, and judged by the investigator as likely to be able to continue to travel for the duration of the study.

• Availability and willingness of a caregiver, informant, or family member to provide input at study visits assessing Clinician's Interview-Based Impression of Change (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Problem Behaviors Assessment-Short form (PBA-s) and Huntington's Disease Quality of Life (HD-QoL). A caregiver is recommended to be someone who attends to the participant at least 2 to 3 times per week for at least 3 hours per occasion, and the suitability of the caregiver should be judged by the investigator.

• For participants taking allowed antidepressant medication, the dosing of medication must have been kept constant for at least 30 days before baseline and must be kept constant during the study.

  • Additional criteria may apply, please contact the investigator for more information.

Exclusion Criteria:

• Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azatioprine within 12 months prior to screening.

• Previous use of laquinimod.

• Use of moderate/strong inhibitors of cytochrome P450 (CYP)3A4 within 2 weeks prior to randomization.

• Use of inducers of CYP3A4 within 2 weeks prior to randomization.

• Pregnant or breastfeeding.

• Participants with a clinically significant or unstable medical or surgical condition that may put the participant at risk when participating in the study or may influence the results of the study or affect the participant's ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests. Such conditions may include:

  • A major cardiovascular event (for example; myocardial infarction, acute coronary syndrome, de-compensated congestive heart failure, pulmonary embolism, coronary revascularization) that occurred prior to randomization.
  • Any acute pulmonary disorder.
  • A central nervous system (CNS) disorder other than HD that may jeopardize the participant's participation in the study, including such disorders that are demonstrated on the baseline MRI (based on local read).
  • A gastrointestinal disorder that may affect the absorption of study medication.
  • Acute or chronic renal disease including acute kidney injury (AKI).
  • Any form of acute or chronic liver disease.
  • Known human immunodeficiency virus (HIV) positive status. Participants will undergo an HIV test at screening per local requirements, if applicable.
  • Any malignancies, excluding basal cell carcinoma, in the 5 years prior to randomization.

• Any clinically significant, abnormal, screening laboratory result which in the opinion of the investigator, affects the participant' suitability for the study or puts the participant at risk if he/she enters the study.

• Unsuitable for MRI (for example; claustrophobia, metal implants).

• Alcohol and/or drug abuse within the 12 months prior to screening, as defined by Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Text Revision (DSM IV TR) criteria for substance abuse.

• Participants with active suicidal ideation during the past month as measured by a most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent) on the baseline screening Columbia-Suicide Severity Rating Scale (C-SSRS) or participants who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) if the attempt or acts were performed within 1 year of screening, or participants who, in the opinion of the investigator, present a serious risk of suicide.

• Participants with known intracranial neoplasms, vascular malformations, or intracranial hemorrhage.

• Known drug hypersensitivity that would preclude administration of laquinimod or placebo, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.

• Swallowing difficulties that would preclude administration of laquinimod or placebo capsules.

• Treatment with any investigational product within 30 days of screening or participants planning to participate in another clinical study assessing any investigational product during the study. Participants in non-interventional and/or observational studies will not be excluded from participating in this study.

• Treatment with tetrabenazine within 30 days of the study baseline visit.

• Treatment with antipsychotic medication within 30 days of the study baseline visit.

  • Additional criteria may apply, please contact the investigator for more information