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Alzheimer's Association International Conference (AAIC) · 2024:Poster Tue-17 · Hendrix, Dickson et al.
Companies recently identified clinical study sites engaging in fraudulent practices, reducing success in Alzheimer's disease (AD) clinical trials. Successful trials are reliable…
When the sample size a conventional design demands is larger than the trial you can run, a Global Statistical Test lets the clinical-endpoint hypotheses be tested anyway. The paper sets out when GST applies, how it is pre-specified, and how it has been received in review.
3 publications
Sorted newest first
2019 · Alzheimer's & Dementia
Background: Amylyx has developed a novel therapeutic, AMX0035, for the treatment of neurodegenerative disease. AMX0035 is a proprietary combination of two small molecule compounds, Sodium Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), de-signed to promote neuronal viability through simultaneous inhibition of ER stress and mitochondrial stress. PB and TUDCA have been evaluated separately in in vitro and in vivo models of Alzheimer’s disease (AD), and clinical trials in amyotrophic lateral sclerosis, Parkinson’s disease and Huntington’s disease. Amylyx discovered a synergy between these two compounds when administered together in a particular range of ratios across multiple preclinical models. Recruitment for the clinical trial began in late 2018. Methods: The study will evaluate safety, tolerability, and biomarkers of molecular target engagement, AD pathology, neurodegeneration and neurophysiology that indicate AMX0035 target engagement and neurobiological effects over 24 weeks. This will be a 6-month, parallel-group, randomized, double-blind, placebo-controlled study of people with late mild cognitive impairment (MCI) or early to moderate dementia due to AD. Participants in the active treatment arm will receive 3g of PB and 1g TUDCA administered orally twice daily. Results: Participants will be evaluated at Poster Presentations: Wednesday, July 17, 2019P1282baseline and at week 24 with multi-sequence structural and functional MRI to assess changes in regional brain volumes (T1), cerebral perfusion (ASL), functional connectivity (BOLD) and cerebrovascular pathology (FLAIR, SWI). Lumbar punctures will be performed at baseline and 24 weeks for selected CSF biomarkers including: amyloid-b1-42, tau, neurofilament light chain (NfL), and markers of mitochondrial redox, HDAC activity, neuronal injury, and neuroinflammation. Patients will be evaluated at weeks 1, 6,12, 18, and 24 for safety, tolerability, and changes in symptoms, as measured with the ADAS-Cog 13, ADCS-ADL, and NPI. Conclusions: This early phase trial is designed to evince target engagement, neurobiological effects, safety and tolerability of AMX0035with multiple objective endpoints including, standard clinical assessments and both established and novel biomarkers associated with neurocognitive impairment. Data will help determine whether to advance AMX0035 to a larger study to establish efficacy and safety and inform choices in study design, patient characteristics and outcome measures.
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