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

Huntington's Disease Clinical Trial

— LEGATO-HD  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02215616
• Other study ID #: TV5600-CNS-20007
• Secondary ID: 2014-000418-75
• Status: Completed
• Phase: Phase 2
• Start date: October 28, 2014
• Est. completion date: June 19, 2018

Study information

• Verified date: April 2020
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: June 19, 2018
• Est. primary completion date: June 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• Laquinimod
Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.
• Placebo
Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.

Locations

Country	Name	City	State
Canada	Teva Investigational Site 11124	Edmonton
Canada	Teva Investigational Site 11118	Ottawa	Ontario
Canada	Teva Investigational Site 11079	Toronto	Ontario
Canada	Teva Investigational Site 11080	Vancouver	British Columbia
Czechia	Teva Investigational Site 54108	Prague
Germany	Teva Investigational Site 32480	Berlin
Germany	Teva Investigational Site 32482	Bochum
Germany	Teva Investigational Site 32618	Erlangen
Germany	Teva Investigational Site 32483	Munchen
Germany	Teva Investigational Site 32481	Munster
Germany	Teva Investigational Site 32479	Ulm
Italy	Teva Investigational Site 30168	Bologna
Italy	Teva Investigational Site 30098	Milano
Italy	Teva Investigational Site 30100	Milano
Italy	Teva Investigational Site 30097	Napoli
Italy	Teva Investigational Site 30099	San Giovanni Rotondo
Netherlands	Teva Investigational Site 38066	Leiden
Portugal	Teva Investigational Site 36026	Lisboa
Russian Federation	Teva Investigational Site 50379	Kazan
Russian Federation	Teva Investigational Site 50380	Moscow
Russian Federation	Teva Investigational Site 50381	Nyznij Novgorod
Spain	Teva Investigational Site 31185	Barakaldo
Spain	Teva Investigational Site 31097	Barcelona
Spain	Teva Investigational Site 31110	Barcelona
Spain	Teva Investigational Site 31186	Burgos
Spain	Teva Investigational Site 31131	Madrid
Spain	Teva Investigational Site 31187	Sevilla
United Kingdom	Teva Investigational Site 34176	Aberdeen
United Kingdom	Teva Investigational Site 34177	Birmingham
United Kingdom	Teva Investigational Site 34194	Liverpool
United Kingdom	Teva Investigational Site 34179	London
United Kingdom	Teva Investigational Site 34203	London
United Kingdom	Teva Investigational Site 34204	London
United Kingdom	Teva Investigational Site 34209	London
United Kingdom	Teva Investigational Site 34175	Manchester
United Kingdom	Teva Investigational Site 34215	Newcastle-Upon-Tyne
United Kingdom	Teva Investigational Site 34216	Sheffield
United States	Teva Investigational Site 12574	Baltimore	Maryland
United States	Teva Investigational Site 12575	Englewood	Colorado
United States	Teva Investigational Site 12571	Golden Valley	Minnesota
United States	Teva Investigational Site 12815	Houston	Texas
United States	Teva Investigational Site 13326	Iowa City	Iowa
United States	Teva Investigational Site 12576	Kirkland	Washington
United States	Teva Investigational Site 12566	La Jolla	California
United States	Teva Investigational Site 12565	Los Angeles	California
United States	Teva Investigational Site 13489	Memphis	Tennessee
United States	Teva Investigational Site 13325	Nashville	Tennessee
United States	Teva Investigational Site 12570	New York	New York
United States	Teva Investigational Site 12569	Rochester	New York
United States	Teva Investigational Site 12572	Saint Louis	Missouri
United States	Teva Investigational Site 12567	San Francisco	California
United States	Teva Investigational Site 13490	Tampa	Florida
United States	Teva Investigational Site 12568	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Italy,  Netherlands,  Portugal,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in UHDRS-TMS at Week 52	UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.	Baseline, Week 52
Secondary	Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52	Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.	Baseline, Week 52