about the study
Legato is a multicenter, multinational, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of laquinimod as treatment in patients with Huntington's Disease.
about the experimental drug
Laquinimod enters the brain, crossing the blood-brain barrier, a natural barrier that protects the brain from many substances circulating in the blood. It has been tested also in the treatment of Multiple Sclerosis. Preclinical animal studies have shown that laquinimod increases the amount of a substance called brain-derived neurotrophic factor (BDNF) and prevents programmed cell death. BDNF is essential for the survival of nerve cells, and it is present at lower than normal levels in patients with Huntington’s. Laquinimod also reduces inflammation, which is a possible underlying mechanism that causes the death of nerve cells in Huntington’s disease.
study sites
The study has involved 53 sites in 10 countries (United States, Canada, Czech Republic, Germany, Italy, the Netherlands, Portugal, Russia, Spain and the United Kingdom).
Number of participants: 352
drug administration
Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.
Participants received tree different dosages: 0.5 milligrams (mg), 1 mg, 1,5 mg
From January 10th 2016, following the recommendation of the Data Safety Monitoring Board, the treatment with a dose of 1.5 mg of laquinimod has been suspended as a safety measure.
inclusion criteria
Patients with symptoms in early stage.
- 36-49 cytosine-adenosine-guanine (CAG) repeats
- Male or female between 21-55 years of age, inclusive, with an onset of HD at or after 18 years of age.
- A sum of greater than (>) 5 points on the UHDRS-TMS at the screening visit.;
- Total Functional Capacity (TFC) ≥ 8;
duration
Started in October 2014, closed in June 2018.
why the study didn't reach phase 3
The main objective of the study was to evaluate the efficacy of laquinimod after 52 weeks of therapy in reducing the motor symptoms of Huntington's patients. Unfortunately, this goal was not achieved as the group of patients taking the drug showed no significant differences compared to the one taking the placebo. This is the reason why the trail didn't start a phase 3. However, the trial's secondary objective was to evaluate the reduction of brain atrophy after 52 weeks of treatment. Patients taking the drug showed a reduction in atrophy in some brain regions (caudate, white matter and overall brain atrophy) compared to the group of patients who took the placebo. This result unfortunately wasn't considered sufficient to start a phase 3 of the trail.
For further information: clinicatrials.gov
