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Huntington's DiseasePhase 2LEGATO-HDNCT02215616

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

A Phase 2 study testing Laquinimod in people with Huntington's Disease, run by Teva Branded Pharmaceutical Products R&D, Inc. at 53 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 21 to 55 years
Conditions the study is for
Huntington's Disease
What is being tested?
Laquinimod
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
352 participants
Where
53 sitesin 10 countries
Study dates
28 Oct 2014to 19 Jun 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

53 sites in 10 countries.

53 sites in 10 countries

United States16 sites

  • Teva Investigational Site 12574

    Baltimore, Maryland, 21287-0005

  • Teva Investigational Site 12575

    Englewood, Colorado, 80113

  • Teva Investigational Site 12571

    Golden Valley, Minnesota, 55427

  • Teva Investigational Site 12815

    Houston, Texas, 77030

  • Teva Investigational Site 13326

    Iowa City, Iowa, 52242

  • Teva Investigational Site 12576

    Kirkland, Washington, 98034

  • Teva Investigational Site 12566

    La Jolla, California, 92037

  • Teva Investigational Site 12565

    Los Angeles, California, 90095

  • Teva Investigational Site 13489

    Memphis, Tennessee, 38163

  • Teva Investigational Site 13325

    Nashville, Tennessee, 37232

  • Teva Investigational Site 12570

    New York, New York, 10032

  • Teva Investigational Site 12569

    Rochester, New York, 14618

  • Teva Investigational Site 12567

    San Francisco, California, 94143

  • Teva Investigational Site 12572

    St Louis, Missouri, 63110

  • Teva Investigational Site 13490

    Tampa, Florida, 33612

  • Teva Investigational Site 12568

    Wichita, Kansas, 67226

Other trials in United States

United Kingdom10 sites

  • Teva Investigational Site 34176

    Aberdeen, AB25 2ZN

  • Teva Investigational Site 34177

    Birmingham, B15 2SG

  • Teva Investigational Site 34194

    Liverpool, L9 7LJ

  • Teva Investigational Site 34179

    London, NW1 2PG

  • Teva Investigational Site 34209

    London, SE1 9RT

  • Teva Investigational Site 34204

    London, SW17 0QT

  • Teva Investigational Site 34203

    London, W12 0NN

  • Teva Investigational Site 34175

    Manchester, M13 9WL

  • Teva Investigational Site 34215

    Newcastle upon Tyne, NE6 4QD

  • Teva Investigational Site 34216

    Sheffield, S5 7AU

Other trials in United Kingdom

Germany6 sites

  • Teva Investigational Site 32480

    Berlin, 10117

  • Teva Investigational Site 32482

    Bochum, 44791

  • Teva Investigational Site 32618

    Erlangen, 91054

  • Teva Investigational Site 32483

    München, 81675

  • Teva Investigational Site 32481

    Münster, 48149

  • Teva Investigational Site 32479

    Ulm, 89081

Other trials in Germany

Spain6 sites

  • Teva Investigational Site 31185

    Barakaldo, 48903

  • Teva Investigational Site 31097

    Barcelona, 8036

  • Teva Investigational Site 31110

    Barcelona, 8041

  • Teva Investigational Site 31186

    Burgos, 09006

  • Teva Investigational Site 31131

    Madrid, 28034

  • Teva Investigational Site 31187

    Seville, 41009

Other trials in Spain

Italy5 sites

  • Teva Investigational Site 30168

    Bologna, 40139

  • Teva Investigational Site 30098

    Milan, 20133

  • Teva Investigational Site 30100

    Milan, 20133

  • Teva Investigational Site 30097

    Naples, 80131

  • Teva Investigational Site 30099

    San Giovanni Rotondo, 71013

Other trials in Italy

Canada4 sites

  • Teva Investigational Site 11124

    Edmonton, T6G 2G3

  • Teva Investigational Site 11118

    Ottawa, Ontario, K1G 4G3

  • Teva Investigational Site 11079

    Toronto, Ontario, M3B 2S7

  • Teva Investigational Site 11080

    Vancouver, British Columbia, V6T 2B5

Other trials in Canada

Russia3 sites

  • Teva Investigational Site 50379

    Kazan', 420101

  • Teva Investigational Site 50380

    Moscow, 125367

  • Teva Investigational Site 50381

    Nyznij Novgorod, 603126

Other trials in Russia

Czechia1 site

  • Teva Investigational Site 54108

    Prague, 12800

Other trials in Czechia

Netherlands1 site

  • Teva Investigational Site 38066

    Leiden, 2333 ZA

Other trials in Netherlands

Portugal1 site

  • Teva Investigational Site 36026

    Lisbon, 1649-035

Other trials in Portugal

About this study

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

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).

Being tested
Laquinimod, Placebo
Medical subject headings
Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LaquinimodDrug

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

  • PlaceboDrug

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

Study groups in NCT02215616
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants will receive 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.
Receives: Drug: Placebo
Laquinimod 0.5 mgExperimentalParticipants will receive 1 capsule of laquinimod 0.5 milligrams (mg) and 2 capsules of matching placebo, orally once daily for 52 weeks.
Receives: Drug: Laquinimod; Drug: Placebo
Laquinimod 1.0 mgExperimentalParticipants 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.
Receives: Drug: Laquinimod; Drug: Placebo
Laquinimod 1.5 mgExperimentalParticipants 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.
Receives: Drug: Laquinimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, Week 52

Secondary outcomes (1)

  1. 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.

    Measured: Baseline, Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2014 (estimated)
  2. Study start28 Oct 2014
  3. Primary completion19 Jun 2018
  4. Study completion19 Jun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
352 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02215616
Sponsor's protocol ID
TV5600-CNS-20007
Other IDs
2014-000418-75, 2014
Acronym
LEGATO-HD
Status last verified
Apr 2020
First submitted
12 Aug 2014
Last updated
4 May 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38280392

  • 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.

    PubMed 27296315

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laquinimod in people with Huntington's Disease, run by Teva Branded Pharmaceutical Products R&D, Inc. at 53 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, United Kingdom, Germany, Spain, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in UHDRS-TMS at Week 52 (time frame: Baseline, Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02215616, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2020.

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