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J05 Legato-hd study: a phase 2 study assessing the efficacy and safety of laquinimod as a treatment for huntington disease
  1. Ralf Reilmann1,
  2. Mark Forrest Gordon2,
  3. Karen E Anderson3,
  4. Andrew Feigin4,
  5. Sarah J Tabrizi5,
  6. Blair R Leavitt6,
  7. Julie C Stout7,
  8. Paola Piccini8,
  9. Gail Rynkowski2,
  10. Rita Volkinshtein2,
  11. Juha Savola2
  1. 1George-Huntington-Institute Muenster & Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research University of Tuebingen, Germany
  2. 2Research and Development Teva Pharmaceuticals Ltd, Frazer PA USA
  3. 3MedStar Georgetown University Hospital & Georgetown University Medical Center Washington DC, USA
  4. 4NYU Langone Health New York, NY, USA
  5. 5UCL Institute of Neurology London, UK
  6. 6Centre for Molecular Medicine and Therapeutics University of British Columbia, Vancouver BC CAN
  7. 7Monash University Melbourne Australia
  8. 8Imperial College London UK

Abstract

Introduction Laquinimod (Teva Pharmaceuticals) is an orally active small molecule that passively enters the blood brain barrier and has been shown to upregulate BDNF secretion and modulate CNS-resident inflammatory pathways involved in pathology of HD. The LEGATO-HD study originally included three dose arms, 0.5 mg, 1.0 mg and 1.5 mg versus placebo in a 12-month multicenter double blind phase 2 study in patients with HD. Cardiovascular safety concerns were observed in multiple sclerosis studies with laquinimod doses of 1.2 mg and 1.5 mg. Although no similar concern was identified in LEGATO-HD, Teva discontinued the 1.5 mg arm in January 2016 as a precautionary safety measure and continued to evaluate the efficacy and safety of the 0.5 mg and 1.0 mg doses.

Aims Evaluate the efficacy and safety of laquinimod in patients with Huntington Disease (HD).

Methods Efficacy assessments include the primary endpoint, change from baseline in Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS) at month 12, and the secondary endpoint, percent change in caudate volume at month 12. Safety measures include adverse event reporting, clinical laboratory tests, vital signs, ECGs, physical examinations, and suicidality (C-SSRS).

Results LEGATO-HD is fully enrolled with 352 patients randomized and is expected to complete in June 2018. Baseline mean (SD) pooled demographics of enrolled patients include females n=172 (49.1%), males n=178 (50.9%), age 44.4(7.6) years, UHDRS-TMS 24.3(13.1), UHDRS-Total Functional Capacity (TFC) 11.1(1.7), and UHDRS-Functional Assessment (FA) 22.7(2.4). The results of the primary and secondary efficacy endpoints and safety measures will be presented at the conference.

Conclusion There is a significant unmet medical need to ameliorate the progression of symptoms and the neurodegeneration in HD. LEGATO-HD provides valuable information towards understanding the efficacy and safety of laquinimod as a potential treatment for patients with HD.

The LEGATO-HD Study is sponsored by Teva Pharmaceuticals Ltd in collaboration with HSG and EHDN and is registered as NCT02215616-clinicaltrials.gov and 2014–000418–75-EudraCT.

  • Huntington disease
  • laquinimod
  • neuroinflammation

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