ALZ-801 for Early Alzheimer's Disease

(APOLLOE4-LTE Trial)

Not currently recruiting at 71 trial locations

Overseen By Richard Holub

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the oral medication ALZ-801 is safe and effective over the long term for individuals with early Alzheimer's disease who possess the APOE4/4 genotype, a genetic profile associated with Alzheimer's. Participants will take an ALZ-801 tablet twice daily. Those who completed a previous study with ALZ-801 and have a reliable partner to help monitor their abilities may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment for Alzheimer's.

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.

Is there any evidence suggesting that ALZ-801 is likely to be safe for humans?

Research has shown that ALZ-801 has been tested in individuals with early Alzheimer's disease, particularly those with the APOE4/4 genetic type. In earlier studies, participants generally tolerated the treatment well.

For instance, studies found that those taking ALZ-801 did not experience serious side effects. The most common side effects were mild, such as headaches or nausea, and were temporary and manageable for most individuals.

This treatment is in a late stage of testing, indicating it has already passed earlier safety checks, suggesting it is likely safe. However, since individual reactions can vary, it is important to consider possible side effects and discuss them with healthcare professionals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard Alzheimer's treatments that mainly focus on managing symptoms, ALZ-801 targets the disease more directly by inhibiting the formation of toxic amyloid-beta oligomers, which are believed to play a key role in the development of Alzheimer's. This mechanism is different from current options, like cholinesterase inhibitors and NMDA receptor antagonists, which aim to boost neurotransmitter activity rather than address underlying disease processes. Researchers are excited about ALZ-801 because it has the potential to modify the disease course, offering hope for slowing progression rather than just alleviating symptoms.

What evidence suggests that ALZ-801 might be an effective treatment for early Alzheimer's disease?

Research has shown that ALZ-801, also known as valiltramiprosate, might slow early Alzheimer's disease, particularly in individuals with the APOE4/4 genetic type. One study found that patients taking ALZ-801 experienced a promising slowdown in memory and thinking problems, although not all results reached statistical significance. Studies using biomarkers (measurable signs of disease) also suggest it could alter disease progression. Additionally, ALZ-801 has demonstrated safety, making it a potentially good option for those at high risk. Overall, the evidence suggests that ALZ-801 could benefit early Alzheimer's patients with specific genetic profiles. ^{3 4 6 7 8}

Who Is on the Research Team?

Susan Abushakra, MD

Principal Investigator

Alzheon Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. alzheon.com alzheon.com/alzheon-announces-peer-reviewed-scientific-publication-of-results-from-pivotal-apolloe4-phase-3-trial-of-oral-valiltramiprosate-alz-801-in-apoe4-4-homozygous-individuals-with-early-alzheimers/

Alzheon Announces Peer-Reviewed Scientific Publication ... This publication provides an overview of effects of valiltramiprosate in the APOLLOE4 Phase 3 trial in patients with Early AD, comprised of Mild ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11712856/

Phase 2 Study Results of Oral ALZ‐801 (Valiltramiprosate) ... These biomarker results support the disease‐modifying effects of ALZ‐801 in Early AD with promising clinical efficacy and favorable safety in APOE4 carriers.

3. foxnews.com foxnews.com/health/alzheimers-pill-could-reduce-brain-decline-some-high-risk-patients-trial-suggests

Alzheimer's pill could reduce brain decline in some high- ... In the overall group, ALZ-801 showed some slowing of memory and cognitive decline, but the difference wasn't statistically significant. Senior ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04693520

Biomarker Effects of ALZ-801 in APOE4 Carriers With Early ... Study Overview. The study will investigate the effects of oral ALZ-801, in subjects with Early AD who have the APOE4/4 or APOE3/4 genotype, on the biomarkers ...

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12498

APOLLOE4 Phase 3 study of oral ALZ‐801/valiltramiprosate in ... The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41015981/

Clinical Efficacy, Safety and Imaging Effects of Oral ... - PubMed Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEε4/ε4 Homozygotes with Early Alzheimer's Disease: Results of the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04770220

NCT04770220 | An Efficacy and Safety Study of ALZ-801 in ... This study is being conducted to evaluate the safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is a ...

8. alzheon.com alzheon.com/pipeline/alz-801-development/

ALZ-801 Development ALZ-801, an orally administered prodrug of tramiprosate designed to inhibit amyloid oligomer formation, a key driver of Alzheimer's disease.