A Clinical Study in Participants With Huntington's Disease (HD) to Assess Efficacy and Safety of Three Oral Doses of Laquinimod

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02215616
• Date of registration: 12/08/2014
• Prospective Registration: Yes
• Primary sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Public title: A Clinical Study in Participants With Huntington's Disease (HD) to Assess Efficacy and Safety of Three Oral Doses of Laquinimod LEGATO-HD
• Scientific title: A Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Laquinimod (0.5, 1.0 and 1.5 mg/Day) as Treatment in Patients With Huntington's Disease
• Date of first enrolment: October 28, 2014
• Target sample size: 352
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02215616
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Canada, Czech Republic, Czechia, France, Germany, India, Israel, Italy, Netherlands, Portugal, Russian Federation, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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



Age minimum: 21 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Huntington's Disease

Intervention(s)

Drug: Placebo

Drug: Laquinimod

Primary Outcome(s)

Change From Baseline in UHDRS-TMS at Week 52 [Time Frame: Baseline, Week 52]

Secondary Outcome(s)

Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52 [Time Frame: Baseline, Week 52]

Secondary ID(s)

TV5600-CNS-20007

2014-000418-75

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02215616