NCT02215616: LEGATO-HD

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

Completed Phase 2 Results posted Last updated 4 May 2020

What this trial tests

Phase 2 trial testing Laquinimod in Huntington's Disease in 352 participants. Completed in 19 June 2018.

Timeline

28 October 2014

Primary endpoint
19 June 2018

19 June 2018

Quick facts

Lead sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	352
Start date	28 October 2014
Primary completion	19 June 2018
Estimated completion	19 June 2018
Sites	53 locations across Italy, Netherlands, Russia, United Kingdom, Germany, Canada, Portugal, United States

Drugs / interventions tested

• Laquinimod (LAQUINIMOD) — full drug profile →
• Placebo

Conditions studied

• Huntington's Disease — all drugs for Huntington's Disease →

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

Adults 21 to 55, any sex, with Huntington's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in UHDRS-TMS at Week 52 Primary · Baseline, 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 supinat

Group	Value	95% CI
Placebo	1.3	± 8.00
Laquinimod 0.5 mg	1.4	± 8.34
Laquinimod 1.0 mg	2.0	± 7.27
Laquinimod 1.5 mg	11.0	± 7.12

Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52 Secondary · Baseline, 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.

Group	Value	95% CI
Placebo	5.13	± 3.265
Laquinimod 0.5 mg	4.03	± 3.275
Laquinimod 1.0 mg	3.14	± 3.360
Laquinimod 1.5 mg	4.11	± 0.598

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 56. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 8/108 (7%)

Deaths: 1/108

Laquinimod 0.5 mg

Serious: 7/107 (7%)

Deaths: 0/107

Laquinimod 1.0 mg

Serious: 5/106 (5%)

Deaths: 0/106

Laquinimod 1.5 mg

Serious: 1/29 (3%)

Deaths: 0/29

Serious adverse events (29 terms)

Reaction	System	Placebo	Laquinimod 0.5 mg	Laquinimod 1.0 mg	Laquinimod 1.5 mg
Defect conduction intraventricular	Cardiac disorders	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—
Burn infection	Infections and infestations	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Gastrointestinal viral infection	Infections and infestations	—	—	—	—
Osteomyelitis chronic	Infections and infestations	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—	—
Multiple injuries	Injury, poisoning and procedural complications	—	—	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—	—	—
Traumatic liver injury	Injury, poisoning and procedural complications	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cluster headache	Nervous system disorders	—	—	—	—
Device dislocation	Product Issues	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—
Psychiatric decompensation	Psychiatric disorders	—	—	—	—
Psychotic disorder	Psychiatric disorders	—	—	—	—
Suicide attempt	Psychiatric disorders	—	—	—	—

Other adverse events (27 terms — click to expand)

Reaction	System	Placebo	Laquinimod 0.5 mg	Laquinimod 1.0 mg	Laquinimod 1.5 mg
Nasopharyngitis	Infections and infestations	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Amylase increased	Investigations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Blood folate decreased	Investigations	—	—	—	—
Irritability	Psychiatric disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Haemoglobin decreased	Investigations	—	—	—	—
Chorea	Nervous system disorders	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—
Pancreatic enzymes increased	Investigations	—	—	—	—
Balance disorder	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Defect conduction intraventricular, Gastrooesophageal reflux disease, Small intestinal obstruction, Cholecystitis, Burn infection, Diverticulitis, Gastroenteritis, Gastrointestinal viral infection.

Data from ClinicalTrials.gov NCT02215616 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Role of Microglia and Astrocytes in Huntington's Disease.
   Palpagama TH, Waldvogel HJ, Faull RLM, Kwakowsky A. · · 2019 · cited 169× · PMID 31708741 · DOI 10.3389/fnmol.2019.00258
2. Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.
   Coppen EM, Roos RA. · · 2017 · cited 90× · PMID 27988871 · DOI 10.1007/s40265-016-0670-4
3. From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research.
   Jiang A, Handley RR, Lehnert K, Snell RG. · · 2023 · cited 88× · PMID 37629202 · DOI 10.3390/ijms241613021
4. Neuroimmunology of Huntington's Disease: Revisiting Evidence from Human Studies.
   Rocha NP, Ribeiro FM, Furr-Stimming E, Teixeira AL. · · 2016 · cited 70× · PMID 27578922 · DOI 10.1155/2016/8653132
5. Current and Possible Future Therapeutic Options for Huntington's Disease.
   Ferguson MW, Kennedy CJ, Palpagama TH, Waldvogel HJ, et al · · 2022 · cited 66× · PMID 35615642 · DOI 10.1177/11795735221092517
6. Therapy development in Huntington disease: From current strategies to emerging opportunities.
   Dickey AS, La Spada AR. · · 2018 · cited 61× · PMID 29218782 · DOI 10.1002/ajmg.a.38494
7. Neuroinflammation in Huntington's disease: From animal models to clinical therapeutics.
   Jia Q, Li S, Li XJ, Yin P. · · 2022 · cited 48× · PMID 36618375 · DOI 10.3389/fimmu.2022.1088124
8. Huntington’s Disease Clinical Trials Corner: February 2018
   Rodrigues FB, Wild EJ. · · 2018 · cited 45× · PMID 29480210 · DOI 10.3233/jhd-189001