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Abstract Details

The Efficacy and Safety Results of Laquinimod as a Treatment for Huntington Disease (LEGATO-HD)
Movement Disorders
S16 - Huntington's Disease: From Bench to Clinical Trials (2:06 PM-2:17 PM)
007

Laquinimod has been shown to modulate CNS-resident inflammatory pathways involved in the pathology of HD.

 

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

LEGATO-HD compared three dose arms (0.5, 1.0, and 1.5 mg once daily) versus placebo in a 52 week phase 2 study in patients with early HD. Cardiovascular safety concerns were observed in multiple sclerosis studies with laquinimod 1.2mg and 1.5mg doses. Although no similar concern was identified in LEGATO-HD, Teva discontinued the 1.5mg arm in 2016 as a precautionary safety measure and continued to evaluate 0.5 and 1.0mg doses. Primary endpoint was change from baseline in Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS) and secondary endpoint was percent change in caudate volume (CV), both for 1.0mg dose group vs placebo at week 52. Exploratory endpoints included changes in MRI volume measures and Quantitative (Q) Motor, CIBIC-Plus, UHDRS-Total Functional Capacity (TFC) and UHDRS-Functional Assessment (FA) scores. Primary and secondary endpoints were under Type I error control, whereas exploratory endpoints were not. Safety measures included adverse event reporting, clinical and laboratory examinations.

 

 The study did not meet its primary endpoint of change from baseline in UHDRS-TMS (p=0.4853), but met its secondary endpoint of percent change in CV loss (p=0.0002). There were treatment effect differences between the laquinimod-treated and placebo-treated patients for all MRI exploratory measures. There were no treatment effects seen in rater-dependent clinical outcome measures. Certain Q-Motor rater-independent assessments (such as tap speed inter-onset-interval of the hands) provided evidence for treatment effect. Laquinimod was well tolerated and there were no new safety findings.

 

 While laquinimod treatment resulted in reduced volume losses in caudate and other brain regions for early HD patients, there was no evidence of improved rater-dependent clinical outcomes in the LEGATO-HD study.

Authors/Disclosures
Ralf Reilmann, MD, FAAN (George-Huntington-Institute)
PRESENTER
The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for uniQure. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WAVE. Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for WAVE. The institution of Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for IOS-Press. The institution of Dr. Reilmann has received research support from European Union. Dr. Reilmann has a non-compensated relationship as a Executive Committee Member with Huntington Study Group that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Member of Executive Committee with European Huntington Disease Network that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Co-Chair Task Force on Huntington Disease with Movement Disorders Socitey that is relevant to AAN interests or activities.
Mark F. Gordon, MD, FAAN (Teva Pharmaceuticals) Dr. Gordon has received personal compensation for serving as an employee of Teva. Dr. Gordon has stock in Teva.
Karen E. Anderson Ms. Anderson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for teva. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AskBio. The institution of Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for novartis. The institution of Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Biogen. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. The institution of Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Ms. Anderson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for neurocrine. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medscape. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for atheneum. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GLG. Ms. Anderson has received personal compensation in the range of $500-$4,999 for serving as a scientific advisor with CHDI.
Andrew S. Feigin, MD (NYU Langone Health) Dr. Feigin has received personal compensation for serving as an employee of Rho, Inc.. Dr. Feigin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kenai. Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ADCS/ATRI. Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. The institution of Dr. Feigin has received research support from Huntngton Study Group. The institution of Dr. Feigin has received research support from Prilenia.
Sarah J. Tabrizi, MD, PhD Sarah J. Tabrizi, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for F. Hoffmann-La Roche Ltd. Sarah J. Tabrizi, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
Blair Leavitt, MD (University of British Columbia) Dr. Leavitt has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Incisive Genetics. Dr. Leavitt has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Leavitt has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Design TX. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReMix Tx. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sintetica. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Triplet Tx. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Leavitt has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Incisive Genetics. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Huntington's Disease. Dr. Leavitt has stock in Incisive Genetics. Dr. Leavitt has stock in SRNAlytics. The institution of Dr. Leavitt has received research support from CIHR. The institution of Dr. Leavitt has received research support from HSC. The institution of Dr. Leavitt has received research support from Brain Canada. The institution of Dr. Leavitt has received research support from NMIN. Dr. Leavitt has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Paola Piccini, MD (Hammersmith Hospital) No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Juha M. Savola, MD, PhD (Spark Therapeutics, Inc) Dr. Savola has received personal compensation for serving as an employee of Teva Pharmaceuticals. Dr. Savola has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file