ASN51 for Alzheimer's Disease

No longer recruiting at 6 trial locations

Overseen By Asceneuron Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Asceneuron S.A.

Must not be taking: Anti-amyloid, Anti-tau therapies

Disqualifiers: Substance abuse, Stroke, Parkinson's, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ASN51 for individuals with early Alzheimer's disease to evaluate its safety and effectiveness. Participants will receive either a low or high dose of ASN51 or a placebo, taken orally each day for up to 24 weeks. The study aims to understand ASN51's impact on disease markers and symptoms. Suitable candidates include those diagnosed with early Alzheimer's, either mild cognitive impairment or mild dementia, who have a care partner to assist in tracking their progress. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Do 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.

Is there any evidence suggesting that ASN51 is likely to be safe for humans?

Research has shown that ASN51, a new treatment being tested for early Alzheimer's disease, appears promising in terms of safety and tolerability. In earlier studies, most participants did not experience major issues with ASN51. The side effects were mostly mild to moderate, with no serious health problems directly linked to the treatment.

This trial is in Phase 2, indicating that the treatment has already undergone basic safety testing in humans. This phase focuses on understanding how the drug works in the body and ensuring its safety at various doses. While ASN51 remains under study and complete information is not yet available, current evidence suggests it is relatively safe. Prospective participants should discuss any concerns with the research team or their doctor.

Why do researchers think this study treatment might be promising for Alzheimer's?

Most treatments for Alzheimer's disease, like donepezil and memantine, focus on managing symptoms by boosting neurotransmitter activity. But ASN51 is different because it targets the underlying mechanisms of the disease. Researchers are intrigued by ASN51 because it has a novel approach that could potentially slow the progression of Alzheimer's, rather than just easing symptoms. This treatment uses a unique active ingredient and is administered orally, which could offer a more convenient and effective option for patients. The excitement around ASN51 stems from its potential to change the trajectory of the disease, offering hope beyond current therapies.

What evidence suggests that ASN51 might be an effective treatment for Alzheimer's disease?

Research has shown that ASN51 targets specific brain functions linked to Alzheimer's disease. This trial will evaluate ASN51 in different dosages. The treatment aims to reduce protein build-up and inflammation in the brain, important factors in the disease's progression. Early studies found that ASN51 can improve certain measurable signs of Alzheimer's. Participants taking ASN51 demonstrated positive changes in memory and thinking tests, suggesting potential benefits for these skills. While these results are promising, more research is needed to confirm its effectiveness in larger groups.

Are You a Good Fit for This Trial?

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

Mini-Mental State Examination score of 20 to 28 (inclusive)

Plasma pTau217 result consistent with the presence of amyloid pathology

I have been diagnosed with early-stage Alzheimer's disease.

Exclusion Criteria

Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment (e.g., current history of substance abuse, uncontrolled vitamin B12 deficiency or abnormal thyroid function, stroke or other cerebrovascular condition, normal pressure hydrocephalus, Parkinson's Disease, Lewy body dementia, cerebral amyloid angiopathy, frontotemporal dementia) or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns

I am a woman who could become pregnant.

I have not been treated with any anti-amyloid or anti-tau therapies, or gene therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of ASN51 or placebo once daily

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ASN51

Trial Overview 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.

How Is the Trial Designed?

Group I: ASN51: Low Dose Experimental Treatment 1 Intervention

Participants were to receive low dose of ASN51 orally, once daily (QD) for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period.

Group II: ASN51: High Dose Experimental Treatment 1 Intervention

Participants were to receive high dose of ASN51 orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period.

Group III: Placebo Placebo Group 1 Intervention

Participants were to receive ASN51 matching placebo orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period.

Who Is Running the Clinical Trial?

Asceneuron S.A.

Lead Sponsor

Trials

5

Recruited

210+

Published Research Related to This Trial

The study identified that using the Functional Activities Questionnaire and the Clinical Dementia Rating Sum of Boxes as endpoints can detect significant changes in Alzheimer's disease progression, particularly in patients with Late Mild Cognitive Impairment, suggesting these measures are effective for future trials.

Composite measures showed even greater sensitivity, indicating that using a combination of endpoints could enhance the success rate of Alzheimer's clinical trials by better capturing the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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? Evans, S., McRae-McKee, K., Wong, MM., et al.[2019]

Managing cardiovascular risk factors, maintaining an active lifestyle, and following a Mediterranean diet can help reduce the risk of Alzheimer's disease (AD) and may slow cognitive decline.

Cholinesterase inhibitors (ChEIs) and memantine are effective pharmacologic treatments for AD, improving cognitive function and daily living activities, with treatment tailored to individual patient needs and preferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical algorithm for managing Alzheimer's disease: what, when, and why? Cummings, JL., Isaacson, RS., Schmitt, FA., et al.[2020]

A pathogenic mutation in the PSEN1 gene (c.1027T>C p.Ala285Val) was identified in a Korean patient with early onset Alzheimer's Disease, highlighting the gene's role in the disease's development.

Neuroimaging revealed significant brain changes, including atrophy and increased amyloid deposition, which are consistent with Alzheimer's pathology, suggesting that this mutation may contribute to the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer's Disease. Vo, VG., Pyun, JM., Bagyinszky, E., et al.[2021]

In a study of 58 Alzheimer's disease patients, those with two copies of the ApoE epsilon4 allele experienced earlier onset of dementia and more severe memory loss compared to those with fewer or no epsilon4 alleles.

Despite the genetic differences, the clinical presentation and cognitive deficits among various subgroups of Alzheimer's patients (based on age of onset and familial history) were largely similar, indicating that the disease's clinical characteristics may not vary significantly with these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism. Lehtovirta, M., Soininen, H., Helisalmi, S., et al.[2019]

Selegiline showed a statistically significant but clinically unimportant improvement in cognitive performance and activities of daily living in Alzheimer's patients during the short term (4-17 weeks), based on data from 821 patients across 14 trials.

No long-term benefits were observed, and there were no significant differences in emotional state or overall global response between selegiline and placebo, indicating limited efficacy for this treatment in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. Wilcock, GK., Birks, J., Whitehead, A., et al.[2019]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has significantly enhanced the understanding of Alzheimer's disease progression and improved the efficiency of clinical trials through the analysis of data from 1459 publications, including 291 impactful studies from 2021 to 2022.

Promising plasma biomarkers, such as phosphorylated tau, have been identified for clinical use, and the studies highlight the importance of neuroinflammation and the biological heterogeneity of Alzheimer's disease, which is influenced by genetic and vascular factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022. Veitch, DP., Weiner, MW., Miller, M., et al.[2023]

In a study involving 1,920 patients with mild to moderate Alzheimer's disease, donepezil was found to be well tolerated, with a completion rate of 79% and a favorable safety profile at doses of 5 mg and 10 mg.

While 11% of patients on donepezil withdrew due to adverse events compared to 7% on placebo, the most common side effects were manageable and included nausea and dizziness, with no significant impact on laboratory tests or liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donepezil: tolerability and safety in Alzheimer's disease. Pratt, RD., Perdomo, CA., Surick, IW., et al.[2022]

Deep brain stimulation targeting the fornix (DBS-f) was found to be safe and well tolerated in a study of 42 participants with mild probable Alzheimer's disease over 12 months.

Younger participants (<65 years) showed a significant decline in cognitive function compared to older participants (≥65 years), suggesting that age may influence treatment outcomes and highlighting the need for careful subject selection in Alzheimer's clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease. Targum, SD., Fosdick, L., Drake, KE., et al.[2021]

In a long-term study of 133 patients with mild to moderately severe Alzheimer's disease, donepezil showed initial cognitive improvement over the first 6-9 months, with a slower decline in cognitive function compared to untreated patients over a period of up to 4.9 years.

Donepezil was generally well-tolerated, with mild and transient side effects primarily affecting the nervous and digestive systems, and no evidence of liver damage, making it a safe option for symptomatic treatment of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: final analysis of a US multicentre open-label study. Rogers, SL., Doody, RS., Pratt, RD., et al.[2019]

A 55-year-old woman with a novel PSEN1 mutation exhibited clear biomarkers of familial Alzheimer's disease, including elevated levels of t-tau and p-tau181 in cerebrospinal fluid, and reduced Aβ(42) levels, confirming the mutation's association with Alzheimer's pathology.

Imaging studies, including FDG-PET and FDDNP-PET, revealed significant brain metabolism changes and amyloid pathology, supporting the mutation's role in the early onset of Alzheimer's disease and validating the use of these biomarkers for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. Ringman, JM., Gylys, KH., Medina, LD., et al.[2023]

A novel heterozygous mutation (c.332G > T) in the PSEN1 gene was identified in a Chinese individual with early-onset Alzheimer's disease, suggesting a genetic link to the condition.

Overexpression of the PSEN1 Gly111Val mutation in cell models led to an increased ratio of Aβ42/Aβ40, indicating that this mutation may contribute to the pathogenic mechanisms of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease. Qiu, Q., Jia, L., Wang, Q., et al.[2022]

In a review of safety data from five 18-month Alzheimer's disease trials, common adverse events included dyspnea (5.3%-5.8%), headache (4.0%-5.5%), and constipation (4.3%-4.7%), indicating a consistent profile of side effects among patients taking placebo.

Larger multinational studies showed higher overall discontinuation rates (24.6%-33.0%) compared to smaller studies (8.2%-21.0%), suggesting that study size and geography may influence patient retention and safety outcomes in Alzheimer's trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of Alzheimer's disease populations in Alzheimer's Disease Neuroimaging Initiative and other 18-month studies. Henley, DB., Sundell, KL., Sethuraman, G., et al.[2021]

In a 12-week study involving 97 participants with Alzheimer's disease, donepezil significantly improved cognitive function, as indicated by a 1.8-point increase in Mini-Mental State Examination (MMSE) scores (P < .0001).

The treatment was also associated with a notable improvement in behavioral symptoms, as shown by a 1.8-point reduction in Neuropsychiatric Inventory 8 (NPI-8) scores (P = .043), and was generally safe and well tolerated, with nausea and diarrhea being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil in patients with Alzheimer's disease in assisted living facilities. Rosenblatt, A., Gao, J., Mackell, J., et al.[2018]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

A novel mutation in the PSEN1 gene (F388L) was identified in a Chinese family with early-onset Alzheimer's disease, with an average age of onset at 43 years.

The F388L mutation leads to increased secretion of amyloid-β (Aβ42) and a higher Aβ42/Aβ40 ratio, which is associated with the pathogenesis of familial Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel presenilin 1 mutation (F388L) identified in a Chinese family with early-onset Alzheimer's disease. Zhan, Y., Zheng, H., Wang, C., et al.[2022]

Citations