Date: 2014-09-22
Type of information: Completion of patient enrollment
phase: 3
Announcement: completion of patient enrollment
Company: TauRx Therapeutics (Singapore - UK)
Product: LMTX™ (leuco-methylthioninium)
Action
mechanism: LMTX™ is a tau aggregation inhibitor (TAI). Methylthioninium chloride (MTC) was the first TAI studied by Professor Wischik and colleagues. The drug was tested in vivo in two transgenic mouse models. In both studies, MTC was able to reverse the behavioural and pathological effects arising from tau pathology. The team concluded that MTC had the potential not only to slow the rate of Alzheimer’s progression, but may even halt it and restore neuronal function, particularly at early stages of the disease. This formed the basis for further development of TauRx’s first generation TAI, rember®, and subsequent follow-on molecules. TauRx’s first-generation TAI, rember®, was a proprietary form of MTC and the first TAI to be tested in clinical trials for Alzheimer’s. An improved version with enhanced bioavailability and tolerability has been developed. The result was LMTX™ (leuco-methylthioninium), a completely new chemical entity that delivers the same active moiety into the bloodstream as its predecessor, rember® but in a more efficient manner. The TauRx team has conducted several animal studies evaluating the pharmacokinetic properties and bioavailability of LMTX™. Additionally, they have determined the compound’s efficacy on tau pathology in two tau-transgenic mouse models which produce tau pathology. In these studies, they also measured the brain concentration at which effect on tau pathology is observed, and related this back to plasma levels in humans and plasma and brain levels in pigs.
Disease: mild to moderate Alzheimer's Disease
Therapeutic area: Neurodegenerative diseases
Country: USA, Europe
Trial
details: The TRx-237-005 clinical trial is a Phase III double-blind, placebo-controlled clinical trial designed to assess the safety and efficacy of LMTX™ in up to 700 patients diagnosed with mild Alzheimer's. The study involves approximately 100 clinical sites primarily in the U.S. and Europe. The clinical efficacy measures are the same as the TRx-237-015 trial. In addition reduction in decline in glucose uptake in the temporal lobe is being measured by FDG/PET imaging and reduction in the rate of brain shrinkage shown by MRI.
Latest
news: * On September 22, 2014, TauRx Therapeutics announced it has achieved its target enrolment of 700 subjects with mild Alzheimer's disease into the second of its two Phase III clinical trials of LMTX™, a tau aggregation inhibitor, for the treatment of Alzheimer's disease. This multi-centre, placebo-controlled clinical trial (Protocol TRx-237-005) is aimed at assessing the efficacy of LMTX™ in people diagnosed with mild Alzheimer's disease. The study is also evaluating the safety and pharmacokinetic profile of LMTX™, and incorporates imaging endpoints in all subjects. In July, TauRx announced that the Company had achieved its target enrolment of 833 subjects into its first Phase III clinical trial (Protocol TRx-237-015). The third global study, TauRx's Phase III clinical trial (Protocol TRx-237-007) in patients with behavioural variant frontotemporal dementia (bvFTD), continues to recruit subjects, and is on track to complete enrolment by early 2015. With both clinical trials in Alzheimer's disease now fully recruited, TauRx and its partners are turning their attention towards the bvFTD clinical trial. This Phase III double-blind placebo-controlled study is designed to evaluate the safety and efficacy of LMTX™ in patients diagnosed with behavioural variant Frontotemporal Dementia (bvFTD). The treatment period is 12 months. The study is planned to involve 180 patients and ~70 study sites located in Canada, U.S., U.K., Germany, The Netherlands, Australia and Singapore. The main measures of efficacy are the change in study subjects' performance at the beginning and the end of the study in two commonly used clinical assessments: (1) the Addenbrookes's Cognitive Examination (Revised), known as ACE-R; and (2) the Modified Alzheimer's Disease Cooperative Study – Clinical Global Impression of Change, known as ADCS-CGIC.
