ASN51 for Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Asceneuron S.A.
Prior Safety Data
Trial Summary
What is the purpose of this trial?The main purpose of this study is to evaluate the safety, tolerability, and effect on biomarkers of disease pathophysiology and pathology, pharmacokinetics (PK), and preliminary effects on measures of clinical efficacy of multiple doses of ASN51 in adult participants with early Alzheimer's disease (AD).
What data supports the idea that ASN51 for Alzheimer's Disease is an effective drug?
The available research does not provide specific data on ASN51 for Alzheimer's Disease. Instead, it discusses general strategies for improving Alzheimer's treatment trials and other drugs like selegiline and cholinesterase inhibitors. These drugs have shown some effectiveness in improving cognitive function and daily living activities in Alzheimer's patients. However, there is no direct evidence from the provided information that supports ASN51 as an effective treatment for Alzheimer's Disease.
39111415Is the drug ASN51 a promising treatment for Alzheimer's Disease?
The drug ASN51, also known as ASN121151, is considered promising for Alzheimer's Disease because it targets genetic mutations linked to the disease, potentially helping to manage or slow down its progression.
17101213What safety data is available for ASN51 in Alzheimer's treatment?
The provided research does not contain specific safety data for ASN51 or ASN121151. The studies focus on donepezil and other treatments, not ASN51. Further research or specific clinical trial data for ASN51 would be needed to answer this question.
24568Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on any anti-amyloid or anti-tau therapies, you may not be eligible to participate.
Eligibility Criteria
This trial is for adults with early-stage Alzheimer's Disease. Participants should be in good general health, have a reliable caregiver, and must not be taking certain other medications that affect cognition.Inclusion Criteria
I have been diagnosed with early-stage Alzheimer's disease.
I am between 50 and 80 years old.
Exclusion Criteria
I have not been treated with any anti-amyloid or anti-tau therapies, or gene therapy.
Participant Groups
The study tests ASN51 against a placebo to assess its safety and impact on Alzheimer's biomarkers, how the body processes it, and any potential benefits on cognitive functions.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: ASN51: Low DoseExperimental Treatment1 Intervention
Participants will receive low dose of ASN51 once daily (QD).
Group II: ASN51: High DoseExperimental Treatment1 Intervention
Participants will receive high dose of ASN51 QD.
Group III: PlaceboPlacebo Group1 Intervention
Participants will receive ASN51 matching placebo QD.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
K2 Medical ResearchClermont, FL
K2 Medical Research - The VillagesLady Lake, FL
K2 Medical ResearchMaitland, FL
Alzheimer's Treatment and Research CenterStuart, FL
More Trial Locations
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Who is running the clinical trial?
Asceneuron S.A.Lead Sponsor
References
Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism. [2019]Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease. In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (> or = 65 years), familial late-onset (FLO) (> or = 65 years), sporadic early-onset (SEO) (
Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: final analysis of a US multicentre open-label study. [2019]This multicentre, open-label study evaluated the long-term efficacy and safety of donepezil in the treatment of patients with mild to moderately severe Alzheimer's disease (AD). The 133 patients who entered the study had previously completed a 14-week randomized, double-blind, placebo-controlled study with donepezil. In this open-label study, patients were treated initially with 3 mg per day donepezil, which could be increased to 5, 7 and 10 mg per day in a step-wise fashion. Patients attended the clinic for assessments at 3-week intervals for the first 12 weeks, then subsequently at 12-week intervals for up to 240 weeks (254 cumulative weeks). Efficacy was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinical Dementia Rating-Sum of the Boxes scale (CDR-SB), and data were compared with those predicted for historical untreated AD patients. During the first 6-9 months of the study, mean ADAS-cog and CDR-SB scores showed evidence of clinical improvement from baseline. After this time scores gradually deteriorated. Overall the decline was less than that estimated if this cohort of patients had not been treated. The most common adverse events were related to the nervous and digestive systems, and were generally mild and transient, resolving without the need for dose modifications. There was no evidence of hepatotoxicity. In conclusion, these data demonstrate that donepezil is a well-tolerated, realistic symptomatic treatment for AD over a period of up to 4.9 years. An interim report of the first 98 weeks of the study has been published previously.
The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. [2019]To evaluate the effect of selegiline in the treatment of patients with Alzheimer's disease, in terms of cognitive performance, functional ability, emotional state (including behaviour and mood) and global response. Data Sources The Cochrane database of trials, Embase, Medline and Psychlit. Study Selection Unconfounded, double-blind, randomised trials of selegiline compared with placebo reported before 31 December 1998. Data Extraction The reviewers selected trials for inclusion. Individual patient data were sought, but when these could not be retrieved summary data were extracted from published papers.
Donepezil: tolerability and safety in Alzheimer's disease. [2022]The tolerability and safety of donepezil HCI in patients with mild to moderate Alzheimer's disease (AD) were examined in an integrated analysis of phase II/III placebo-controlled trials. Patients with mild to moderately severe AD (n=1,920) were randomised to receive donepezil (n=1,291) or placebo (n=629). Adverse events, physical examinations and clinical laboratory tests were assessed. A high completion rate (79%) was achieved in these trials. Of the 1,291 patients receiving donepezil only, 142 (11%) withdrew because of an adverse event compared with 43 of the 629 (7%) placebo patients. The most common adverse events included nausea, diarrhoea, headache, insomnia, dizziness, rhinitis, vomiting, asthenia/fatigue and anorexia. Donepezil had no clinically significant effect on any laboratory evaluations and was not associated with hepatotoxicity. These results demonstrate that donepezil is well tolerated and has a favourable safety profile at clinically effective, once-daily doses of 5 mg and 10 mg.
AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]To investigate the efficacy and safety of the positive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 in patients with mild to moderate Alzheimer disease (AD) (Mini-Mental State Examination scores 14 to 26).
Efficacy and safety of donepezil in patients with Alzheimer's disease in assisted living facilities. [2018]The aim of this 12-week, open-label study was to determine the safety and efficacy of donepezil in participants with Alzheimer's disease (AD) residing in assisted living facilities (ALFs). Participants received 5 mg donepezil daily for 6 weeks followed by 10 mg daily for 6 weeks. Primary and secondary outcomes were change from baseline in Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory 8 (NPI-8) scores, respectively. Safety was assessed by adverse events (AEs) and laboratory tests. Of the 97 participants, 76 completed the study. Mean MMSE score (18.7 at baseline) improved 1.8 points (P
Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. [2023]Familial Alzheimer's disease (AD) due to PSEN1 mutations provides an opportunity to examine AD biomarkers in persons in whom the diagnosis is certain. We describe a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who underwent genetic, clinical, biochemical and magnetic resonance and nuclear imaging assessments. We also describe neuropathological findings in her similarly affected brother. Neuropsychological testing confirmed deficits in memory, visuospatial and language function. CSF t-tau and p-tau181 were markedly elevated and Aβ(42) levels reduced. FDG-PET revealed hypometabolism in the left parietotemporal cortex. FDDNP-PET showed increased binding of tracer in medial temporal and parietal lobes and in the head of the caudate and anterior putamen bilaterally. Neuropathological examination of her brother showed the typical findings of AD and the striatum demonstrated amyloid pathology and marked neurofibrillary pathology beyond that typically seen in late-onset AD. A novel S212Y substitution in PSEN1 was present in the index patient and her affected brother but not in an older unaffected sister. An in vitro assay in which the S212Y mutation was introduced in cell culture confirmed that it was associated with increased production of Aβ(42). We describe biochemical, imaging, and neuropathological changes in a pedigree with a novel PSEN1 mutation. This allows us to validate the pathogenicity of this mutation and the indices used to assess AD.
Safety profile of Alzheimer's disease populations in Alzheimer's Disease Neuroimaging Initiative and other 18-month studies. [2021]Demonstration of a disease-modifying effect of a therapeutic agent on Alzheimer's disease (AD) requires a trial lasting for at least 18 months. An understanding of expected rates of adverse events (AEs), overall discontinuations, and discontinuations due to AEs, serious AEs, and deaths would be useful in planning such trials.
A practical algorithm for managing Alzheimer's disease: what, when, and why? [2020]Alzheimer's disease (AD) is the most common form of dementia and its prevalence is increasing. Recent developments in AD management provide improved ways of supporting patients and their caregivers throughout the disease continuum. Managing cardiovascular risk factors, maintaining an active lifestyle (with regular physical, mental and social activity) and following a Mediterranean diet appear to reduce AD risk and may slow cognitive decline. Pharmacologic therapy for AD should be initiated upon diagnosis. All of the currently available cholinesterase inhibitors (ChEIs; donepezil, galantamine, and rivastigmine) are indicated for mild-to-moderate AD. Donepezil (10 and 23 mg/day) and rivastigmine transdermal patch (13.3 mg/24 h) are indicated for moderate-to-severe AD. Memantine, an N-methyl-d-aspartate receptor antagonist, is approved for moderate-to-severe AD. ChEIs have been shown to improve cognitive function, global clinical status and patients' ability to perform activities of daily living. There is also evidence for reduction in emergence of behavioral symptoms with ChEI therapy. Treatment choice (e.g., oral vs. transdermal) should be based on patient or caregiver preference, ease of use, tolerability, and cost. Treatment should be individualized; patients can be switched from one ChEI to another if the initial agent is poorly tolerated or ineffective. Memantine may be introduced in moderate-to-severe disease stages. Clinicians will regularly monitor symptoms and behaviors, manage comorbidities, assess function, educate and help caregivers access information and support, evaluate patients' fitness to drive or own firearms, and provide advice about the need for legal and financial planning. Review of caregiver well-being and prompt referral for support is vital.
A novel presenilin 1 mutation (F388L) identified in a Chinese family with early-onset Alzheimer's disease. [2022]A subset of Alzheimer's disease (AD) occurrence shows autosomal dominant, familial inheritance patterns. Such familial AD (FAD) are caused by mutations in APP, PSEN1, and PSEN2 genes, which encode amyloid-β (Aβ) precursor protein, presenilin 1 (PS1), and presenilin 2 (PS2), respectively. Here, we report a novel PSEN1 mutation (c.1164C > G, p.F388L, mutation nomenclature according to National Center for Biotechnology Information Reference Sequence: NM_000021.3) occurring in a Chinese family with early-onset AD and cosegregating with affected family members. The average age at onset of this family was 43 years. The F388L mutation locates adjacent to the critical catalytic aspartate site (D385) of PS1. Overexpression of the F388L mutant significantly increased Aβ42 secretion and the ratio of Aβ42/Aβ40 when compared with wild type PS1, consisting with the notion that FAD-associated PS1 mutations induce disease pathogenesis by increasing Aβ42/Aβ40 ratio. Our results identify a novel pathogenic PS1 F388L mutation in a Chinese FAD family.
The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment? [2019]To date, Alzheimer's disease (AD) clinical trials have been largely unsuccessful. Failures have been attributed to a number of factors including ineffective drugs, inadequate targets, and poor trial design, of which the choice of endpoint is crucial. Using data from the Alzheimer's Disease Neuroimaging Initiative, we have calculated the minimum detectable effect size (MDES) in change from baseline of a range of measures over time, and in different diagnostic groups along the AD development trajectory. The Functional Activities Questionnaire score had the smallest MDES for a single endpoint where an effect of 27% could be detected within 3 years in participants with Late Mild Cognitive Impairment (LMCI) at baseline, closely followed by the Clinical Dementia Rating Sum of Boxes (CDRSB) score at 28% after 2 years in the same group. Composite measures were even more successful than single endpoints with an MDES of 21% in 3 years. Using alternative cognitive, imaging, functional, or composite endpoints, and recruiting patients that have LMCI could improve the success rate of AD clinical trials.
Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease. [2022]Presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) genes account for the majority of autosomal dominant Alzheimer's disease (AD), with PSEN1 being the most common. We screened these genes for mutations in a Chinese proband from an autosomal dominant early-onset AD pedigree. Early-onset AD is defined as the age at onset of AD < 65 years. A heterozygous variant (c.332G > T) of PSEN1, which results in a missense mutation (p.Gly111Val), was identified. Three prediction programs suggested this mutation was disease causing. When PSEN1 Gly111Val was overexpressed in HEK293/APPswe cells, the ratio of Aβ42/Aβ40 was significantly increased compared with that of wild-type PSEN1. Our results suggest that this novel PSEN1 Gly111Val mutation may play a pathogenic role in AD.
Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer's Disease. [2021]Presenilin 1 (PSEN1) was suggested as the most common causative gene of early onset Alzheimer's Disease (AD).
Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease. [2021]Age may affect treatment outcome in trials of mild probable Alzheimer's disease (AD).
The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022. [2023]The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.