Date: 2016-01-11
Type of information: DSMB assessment
phase: 2
Announcement: treatment of the first patient
Company: Teva Pharmaceutical (Israel) Active Biotech (Sweden)
Product: laquinimod
Action
mechanism: Laquinimod is a once-daily oral, investigational, CNS-active immunomodulator with a novel mechanism of action being developed primarily for the treatment of relapsing-remitting MS (RRMS) and progressive forms of MS. In extensive non-clinical and clinical studies, laquinimod has demonstrated both anti-inflammatory and neuroprotective properties and effects that have been shown to provide clinically meaningful results.
Disease: Huntington's disease
Therapeutic area: Genetic diseases - Neurodegenerative diseases - Rare diseases
Country:
Trial
details: LEGATO-HD (Laquinimod Efficacy and Safety in a GlobAl Trial Of HD) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of laquinimod treatment at doses of 0.5, 1.0, and 1.5 mg/day in 400 adult Huntington’s disease patients between the ages of 21-55. Ancillary studies will evaluate microglia activation, neuronal integrity, and peripheral inflammatory biomarkers. The primary endpoint of LEGATO-HD is change from baseline in the Unified Huntington’s Disease Rating Scale-Total Motor Scale (UHDRS-TMS) as defined by the sum of the scores of all UHDRS-TMS sub-items after 12 months of treatment. Secondary endpoints will measure brain atrophy, cognition, clinical global impression and functional capacity.
Latest
news: * On January 11, 2016, Active Biotech announced that its partner Teva Pharmaceutical Industries will amend the trial design in a Phase 2 study of laquinimod in Huntington’s disease. The amendment consists of dropping the highest of three doses (1.5 mg/day) in the trial while keeping two remaining active doses (0.5 and 1 mg/day) unchanged. This is a precautionary measure in the interest of patient safety being suggested by Teva to the Data Safety Monitory Board (DSMB) for the LEGATO-HD trial. * On August 14, 2014, Active Biotech announced that its partner Teva Pharmaceutical Industries will initiate a phase II clinical trial to evaluate the efficacy and safety of oral laquinimod for the treatment of Huntington\'s disease.
The DSMB accepted the recommendation after reviewing data which observed cardiovascular incidents in patients receiving the high doses of laquinimod in two multiple sclerosis trials as reported on January 4, 2016. No cardiovascular events have been observed for any dose of the LEGATO-HD trial. Teva will continue in its commitment to study laquinimod in Huntington’s disease.
Currently the mechanism of the cardiovascular events in the MS trials remains unknown. Although no specific time-to-event patterns have been identified, cardiovascular risk factors and demographics may play a role.
* On November 4, 2014, Teva Pharmaceutical Industries and Active Biotech announced that Teva has screened the first patient in the LEGATO-HD trial, which will evaluate laquinimod in Huntington’s disease. The LEGATO-HD study will evaluate the efficacy, safety and tolerability of once-daily oral laquinimod as a potential treatment for adult patients with Huntington’s disease. The primary endpoint for LEGATO-HD is change from baseline in the Unified Huntington’s Disease Rating Scale-Total Motor Scale (UHDRS-TMS) as defined by the sum of the scores of all UHDRS-TMS sub-items after 12 months of treatment. Huntington’s disease is caused by a genetically-programmed degeneration of brain cells in select areas of the brain, which results in uncontrolled movements, loss of intellectual faculties and personality and emotional disturbances. LEGATO-HD has an estimated completion date of H1 2017.
