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

NCT02215616 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: TV5600-CNS-200072014-000418-75
• Study Type: interventional
• Target: 352
• Locations: 10 countries
• Sites: 53

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

Outcome Measures

Primary Outcomes (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.

  Baseline, Week 52

Secondary Outcomes (1)

• Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52

  Baseline, Week 52

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Laquinimod 0.5 mg

EXPERIMENTAL

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

Drug: Laquinimod; Drug: Placebo

Laquinimod 1.0 mg

EXPERIMENTAL

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.

Drug: Laquinimod; Drug: Placebo

Laquinimod 1.5 mg

EXPERIMENTAL

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.

Drug: Laquinimod

Interventions

Laquinimod DRUG

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

Laquinimod 0.5 mg; Laquinimod 1.0 mg; Laquinimod 1.5 mg

Placebo DRUG

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

Laquinimod 0.5 mg; Laquinimod 1.0 mg; Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (53)

Teva Investigational Site 12566

La Jolla, California, 92037, United States

Location

Teva Investigational Site 12565

Los Angeles, California, 90095, United States

Location

Teva Investigational Site 12567

San Francisco, California, 94143, United States

Location

Teva Investigational Site 12575

Englewood, Colorado, 80113, United States

Location

Teva Investigational Site 13490

Tampa, Florida, 33612, United States

Location

Teva Investigational Site 13326

Iowa City, Iowa, 52242, United States

Location

Teva Investigational Site 12568

Wichita, Kansas, 67226, United States

Location

Teva Investigational Site 12574

Baltimore, Maryland, 21287-0005, United States

Location

Teva Investigational Site 12571

Golden Valley, Minnesota, 55427, United States

Location

Teva Investigational Site 12572

St Louis, Missouri, 63110, United States

Location

Teva Investigational Site 12570

New York, New York, 10032, United States

Location

Teva Investigational Site 12569

Rochester, New York, 14618, United States

Location

Teva Investigational Site 13489

Memphis, Tennessee, 38163, United States

Location

Teva Investigational Site 13325

Nashville, Tennessee, 37232, United States

Location

Teva Investigational Site 12815

Houston, Texas, 77030, United States

Location

Teva Investigational Site 12576

Kirkland, Washington, 98034, United States

Location

Teva Investigational Site 11080

Vancouver, British Columbia, V6T 2B5, Canada

Location

Teva Investigational Site 11118

Ottawa, Ontario, K1G 4G3, Canada

Location

Teva Investigational Site 11079

Toronto, Ontario, M3B 2S7, Canada

Location

Teva Investigational Site 11124

Edmonton, T6G 2G3, Canada

Location

Teva Investigational Site 54108

Prague, 12800, Czechia

Location

Teva Investigational Site 32480

Berlin, 10117, Germany

Location

Teva Investigational Site 32482

Bochum, 44791, Germany

Location

Teva Investigational Site 32618

Erlangen, 91054, Germany

Location

Teva Investigational Site 32483

München, 81675, Germany

Location

Teva Investigational Site 32481

Münster, 48149, Germany

Location

Teva Investigational Site 32479

Ulm, 89081, Germany

Location

Teva Investigational Site 30168

Bologna, 40139, Italy

Location

Teva Investigational Site 30098

Milan, 20133, Italy

Location

Teva Investigational Site 30100

Milan, 20133, Italy

Location

Teva Investigational Site 30097

Napoli, 80131, Italy

Location

Teva Investigational Site 30099

San Giovanni Rotondo, 71013, Italy

Location

Teva Investigational Site 38066

Leiden, 2333 ZA, Netherlands

Location

Teva Investigational Site 36026

Lisbon, 1649-035, Portugal

Location

Teva Investigational Site 50379

Kazan', 420101, Russia

Location

Teva Investigational Site 50380

Moscow, 125367, Russia

Location

Teva Investigational Site 50381

Nyznij Novgorod, 603126, Russia

Location

Teva Investigational Site 31185

Barakaldo, 48903, Spain

Location

Teva Investigational Site 31097

Barcelona, 8036, Spain

Location

Teva Investigational Site 31110

Barcelona, 8041, Spain

Location

Teva Investigational Site 31186

Burgos, 09006, Spain

Location

Teva Investigational Site 31131

Madrid, 28034, Spain

Location

Teva Investigational Site 31187

Seville, 41009, Spain

Location

Teva Investigational Site 34176

Aberdeen, AB25 2ZN, United Kingdom

Location

Teva Investigational Site 34177

Birmingham, B15 2SG, United Kingdom

Location

Teva Investigational Site 34194

Liverpool, L9 7LJ, United Kingdom

Location

Teva Investigational Site 34179

London, NW1 2PG, United Kingdom

Location

Teva Investigational Site 34209

London, SE1 9RT, United Kingdom

Location

Teva Investigational Site 34204

London, SW17 0QT, United Kingdom

Location

Teva Investigational Site 34203

London, W12 0NN, United Kingdom

Location

Teva Investigational Site 34175

Manchester, M13 9WL, United Kingdom

Location

Teva Investigational Site 34215

Newcastle upon Tyne, NE6 4QD, United Kingdom

Location

Teva Investigational Site 34216

Sheffield, S5 7AU, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38280392 DERIVED

• 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.

  PMID: 27296315 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

laquinimod

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2014
• First Posted: August 13, 2014
• Study Start: October 28, 2014
• Primary Completion: June 19, 2018
• Study Completion: June 19, 2018
• Last Updated: May 4, 2020
• Results First Posted: June 19, 2019

Record last verified: 2020-04

Locations

RU (3); US (16); CA (4); NL (1); IT (5); GB (10); CZ (1); ES (6); DE (6); PT (1)