A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Oral Allopregnanolone (LYT-300) for the Treatment of Premutation Carriers with FXTAS
Abstract
The objectives of this study are to complete a randomized double-blind controlled trial of a new oral formulation of the endogenous neurosteroid, allopregnanolone (LYT-300), in individuals who have the Fragile X-associated Tremor/Ataxia syndrome (FXTAS) to assess the safety and benefit of LYT-300. Our application targets the Fiscal Year 2022 (FY22) Peer Reviewed Medical Research Program (PRMRP) Topic Area of Fragile X and the FY22 PRMRP Strategic Goal to develop and evaluate novel treatments, including research to repurpose existing drugs, for associated neurological diseases and psychological conditions. Our application also addresses development and testing of treatment strategies to manage symptoms and improve quality of life for these conditions. Fragile X refers to a group of disorders, including fragile X syndrome (FXS) and premutation or fragile X carrier disorders, that are caused by different numbers of repeated elements in the Fragile X Mental Retardation 1 (FMR1) gene. FXS and FXTAS are two very different disorders, one causing intellectual disability (ID) and autism and the other leading to neurodegeneration in otherwise normally developed aging individuals, respectively. FXTAS is the most serious of the fragile X spectrum disorders because it is a neurodegenerative disorder that typically begins in FMR1 premutation carriers when they reach the age of about 60. The symptoms of FXTAS include tremor in the hands with action or at rest, and balance problems (ataxia) which leads to frequent falling. Carriers are common in the general population, occurring in 1 in 150 to 200 women and 1 in 400 men, but FXTAS is often mistakenly diagnosed as Parkinson s disease. FXTAS also causes brain atrophy and white matter disease in the brain and for many patients there is cognitive decline that is sometimes misdiagnosed as Alzheimer s disease. A previous clinical trial of IV-administered allopregnanolone showed that weekly infusion of the drug in individuals with FXTAS may improve deficits in executive function, learning, and memory. Effective administration of allopregnanolone has only been possible via intravenous infusion because when given orally almost no drug reaches the blood circulation due to processing by the liver. LYT-300 is designed to use the human body s lipid absorption pathways to bypass the liver and release potentially therapeutically effective amounts of allopregnanolone in the bloodstream. If this medication is helpful in FXTAS, it will likely be beneficial for other types of neurological disorders, and we expect that it could be widely used in the future. This grant proposal includes a planning phase of 1 year to prepare for the trial and submit the U.S. Food and Drug Administration, Investigational New Drug, Institutional Review Board, and Human Research Protection Office applications. In the following 2-year clinical phase, we expect to enroll 50 individuals in a placebo-controlled, parallel-group clinical trial to determine safety, tolerability, and several measures of efficacy. A successful clinical trial in this indication will contribute to ultimate commercialization of LYT-300, which will help military Veterans and others who have FXTAS and other related neurological diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310598
Entities
People
- Michael Chen
Organizations
- United States Army