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

NCT ID: NCT02215616

Last Updated: 2020-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-28
• Study Completion Date: 2018-06-19

Brief 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).

Conditions

Huntington's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Participants will receive 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.

Laquinimod 0.5 mg

Participants will receive 1 capsule of laquinimod 0.5 milligrams (mg) and 2 capsules of matching placebo, orally once daily for 52 weeks.

Group Type: EXPERIMENTAL

Laquinimod

Intervention Type: DRUG

Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.

Placebo

Intervention Type: DRUG

Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.

Laquinimod 1.0 mg

Participants will receive 2 capsule of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.

Group Type: EXPERIMENTAL

Laquinimod

Intervention Type: DRUG

Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.

Placebo

Intervention Type: DRUG

Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.

Laquinimod 1.5 mg

Participants will receive 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily.

Note: The treatment of this high dose arm was discontinued as of 10 January 2016.

Group Type: EXPERIMENTAL

Laquinimod

Intervention Type: DRUG

Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.

Interventions

Laquinimod

Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.

Intervention Type: DRUG

Placebo

Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Teva Investigational Site 12566

La Jolla, California, United States

Teva Investigational Site 12565

Los Angeles, California, United States

Teva Investigational Site 12567

San Francisco, California, United States

Teva Investigational Site 12575

Englewood, Colorado, United States

Teva Investigational Site 13490

Tampa, Florida, United States

Teva Investigational Site 13326

Iowa City, Iowa, United States

Teva Investigational Site 12568

Wichita, Kansas, United States

Teva Investigational Site 12574

Baltimore, Maryland, United States

Teva Investigational Site 12571

Golden Valley, Minnesota, United States

Teva Investigational Site 12572

St Louis, Missouri, United States

Teva Investigational Site 12570

New York, New York, United States

Teva Investigational Site 12569

Rochester, New York, United States

Teva Investigational Site 13489

Memphis, Tennessee, United States

Teva Investigational Site 13325

Nashville, Tennessee, United States

Teva Investigational Site 12815

Houston, Texas, United States

Teva Investigational Site 12576

Kirkland, Washington, United States

Teva Investigational Site 11080

Vancouver, British Columbia, Canada

Teva Investigational Site 11118

Ottawa, Ontario, Canada

Teva Investigational Site 11079

Toronto, Ontario, Canada

Teva Investigational Site 11124

Edmonton, , Canada

Teva Investigational Site 54108

Prague, , Czechia

Teva Investigational Site 32480

Berlin, , Germany

Teva Investigational Site 32482

Bochum, , Germany

Teva Investigational Site 32618

Erlangen, , Germany

Teva Investigational Site 32483

München, , Germany

Teva Investigational Site 32481

Münster, , Germany

Teva Investigational Site 32479

Ulm, , Germany

Teva Investigational Site 30168

Bologna, , Italy

Teva Investigational Site 30098

Milan, , Italy

Teva Investigational Site 30100

Milan, , Italy

Teva Investigational Site 30097

Napoli, , Italy

Teva Investigational Site 30099

San Giovanni Rotondo, , Italy

Teva Investigational Site 38066

Leiden, , Netherlands

Teva Investigational Site 36026

Lisbon, , Portugal

Teva Investigational Site 50379

Kazan', , Russia

Teva Investigational Site 50380

Moscow, , Russia

Teva Investigational Site 50381

Nyznij Novgorod, , Russia

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

Seville, , Spain

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 34209

London, , United Kingdom

Teva Investigational Site 34204

London, , United Kingdom

Teva Investigational Site 34203

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 Kingdom

Countries

United States; Canada; Czechia; Germany; Italy; Netherlands; Portugal; Russia; Spain; United Kingdom

References

Reilmann R, Anderson KE, Feigin A, Tabrizi SJ, Leavitt BR, Stout JC, Piccini P, Schubert R, Loupe P, Wickenberg A, Borowsky B, Rynkowski G, Volkinshtein R, Li T, Savola JM, Hayden M, Gordon MF; LEGATO-HD Study Group. Safety and efficacy of laquinimod for Huntington's disease (LEGATO-HD): a multicentre, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Neurol. 2024 Mar;23(3):243-255. doi: 10.1016/S1474-4422(23)00454-4. Epub 2024 Jan 24.

Reference Type: DERIVED

PMID: 38280392 (View on PubMed)

Ehrnhoefer DE, Caron NS, Deng Y, Qiu X, Tsang M, Hayden MR. Laquinimod decreases Bax expression and reduces caspase-6 activation in neurons. Exp Neurol. 2016 Sep;283(Pt A):121-8. doi: 10.1016/j.expneurol.2016.06.008. Epub 2016 Jun 11.

Reference Type: DERIVED

PMID: 27296315 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-000418-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TV5600-CNS-20007

Identifier Type: -

Identifier Source: org_study_id