ALZ-801 for Early Alzheimer's Disease

(APOLLOE4-LTE Trial)

Recruiting at 71 trial locations

Overseen By Sanjiv Sharma

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alzheon Inc.

Must not be taking: Amyloid antibodies

Disqualifiers: Moderate-severe ARIA, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

285 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being conducted to evaluate the long-term safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is an open-label trial of treatment with ALZ-801.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it mentions that some medications might be prohibited. It's best to discuss your current medications with the trial team to see if any are not allowed.

What data supports the effectiveness of the drug ALZ-801 for early Alzheimer's disease?

ALZ-801, a prodrug of tramiprosate, has shown promise in reducing harmful protein formations in the brain associated with Alzheimer's disease. Studies indicate that it can lower levels of these proteins in the brain fluid, which may help stabilize cognitive function, especially in patients with mild Alzheimer's. ^{1 2 3 4 5}

Is ALZ-801 safe for humans?

ALZ-801, a prodrug of tramiprosate, has been shown to be generally safe and well-tolerated in clinical studies, with improved gastrointestinal tolerability compared to tramiprosate. Some mild-to-moderate nausea and vomiting were noted with tramiprosate, but ALZ-801 was developed to reduce these side effects. ^{1 2 3 4 6}

How does the drug ALZ-801 differ from other Alzheimer's treatments?

ALZ-801 is unique because it is an oral drug that inhibits the formation of beta amyloid oligomers, which are believed to drive neurodegeneration in Alzheimer's disease. It is a prodrug of tramiprosate, designed to improve gastrointestinal tolerability and pharmacokinetic variability, making it more effective and easier to tolerate than its predecessor. ^{1 2 3 4 7}

Research Team

Susan Abushakra, MD

Principal Investigator

Alzheon Inc.

Eligibility Criteria

This trial is for people with early-stage Alzheimer's disease who have a specific genetic makeup (APOE4/4 genotype). It's an extension of a previous study, so participants likely need to have been involved in that earlier phase.

Inclusion Criteria

I have someone who can accurately report on my mental and physical abilities.

I completed Week 78 of the ALZ-801-AD301 study while taking the medication.

Exclusion Criteria

Has received (or plans to receive) amyloid antibodies since completing Phase 3 core study (ALZ-801-AD301)

Significant worsening of medical conditions that may preclude completion of this study

I have new or worsening brain swelling or bleeding shown in scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALZ-801 for 52 weeks, starting with one 265 mg tablet in the evening for the first 4 weeks, then one 265 mg tablet BID

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive ALZ-801 in an open-label setting to evaluate long-term safety and efficacy

Long-term

Treatment Details

Interventions

• ALZ-801

Trial Overview The trial is testing the long-term effects of ALZ-801 on patients. Since it's open-label, everyone knows they're getting the experimental drug and there’s no placebo group.

Participant Groups

Group I: Experimental: ALZ-801 Experimental Treatment 1 Intervention

ALZ-801 265 mg BID tablet orally. Subjects will take one 265 mg tablet of ALZ-801 in the evening during the first 4 weeks of the study; thereafter, they will take one 265 mg tablet BID.

Who Is Running the Clinical Trial?

Alzheon Inc.

Lead Sponsor

Trials

5

Recruited

750+

Findings from Research

ALZ-801, a prodrug of tramiprosate, demonstrated excellent safety and tolerability in a phase I study involving 127 healthy volunteers, with no severe adverse events reported and mild gastrointestinal symptoms that improved with continued use.

The pharmacokinetic profile of ALZ-801 showed significantly reduced variability and a longer elimination half-life compared to tramiprosate, allowing for a clinical dose of 265 mg twice daily to achieve similar exposure levels to 150 mg of tramiprosate, supporting its potential for further development in Alzheimer's disease treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. Hey, JA., Yu, JY., Versavel, M., et al.[2019]

Alzhemed (tramiprosate) is a well-tolerated treatment for mild-to-moderate Alzheimer's disease that effectively reduces levels of the neurotoxic amyloid-beta peptide in the cerebrospinal fluid after 3 months of treatment.

While Alzhemed did not show immediate cognitive improvements after 3 months, long-term follow-up suggested stabilization of cognitive function, particularly in patients with mild Alzheimer's disease, indicating potential benefits over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzhemed: a potential treatment for Alzheimer's disease. Aisen, PS., Gauthier, S., Vellas, B., et al.[2019]

In a study involving 144 subjects with amnestic mild cognitive impairment, AL-108 was found to be generally safe and well tolerated over 12 weeks of treatment.

While the overall efficacy analysis did not show a significant difference in cognitive memory scores between AL-108 and placebo, there were promising signals of potential efficacy in specific memory and attention tasks, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Morimoto, BH., Schmechel, D., Hirman, J., et al.[2016]

In a study involving 41 Alzheimer disease patients, acupuncture alone showed a significant improvement in cognitive function (measured by MMSE) compared to a combination of acupuncture and music therapy.

While both treatments improved patient outcomes, acupuncture alone was found to be more effective than the combination therapy, suggesting that acupuncture may be a stronger intervention for enhancing therapeutic effects in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation on acupuncture combined with music for treatment of Alzheimer disease]. Liu, G., Yuan, LX.[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]

Aducanumab, an antiamyloid antibody, showed modest efficacy in a phase 3 trial for Alzheimer's disease, supporting the amyloid beta hypothesis as a valid therapeutic target despite previous failures in amyloid-targeted treatments.

ALZ-801 is a promising oral drug that effectively penetrates the blood-brain barrier and inhibits the formation of toxic Aβ oligomers, with a phase 3 trial planned for patients with early Alzheimer's disease, specifically targeting those with the APOE4/4 genotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. Tolar, M., Abushakra, S., Sabbagh, M.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. [2019]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Alzhemed: a potential treatment for Alzheimer's disease. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. [2016]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical observation on acupuncture combined with music for treatment of Alzheimer disease]. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. [2021]