ACP-204 for Alzheimer's Disease

Recruiting at 109 trial locations

Overseen By Kristen White

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2 & 3

Sponsor: ACADIA Pharmaceuticals Inc.

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Anti-tau therapy, Donanemab

Disqualifiers: Hospice care, Atrial fibrillation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

1074 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a master protocol for 3 independent, seamlessly enrolling, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in patients with ADP * Substudy 1 (Phase 2) will evaluate efficacy and dose response of ACP-204 30 and 60 mg vs placebo. This substudy will be initiated first. * Substudies 2A and 2B (both: Phase 3) will be confirmatory studies of either both doses (ACP-204 30 and 60 mg, respectively) or a single dose from Part 1 vs placebo. Substudies 2A and 2B will be performed independently of each other and will commence after enrollment of Part 1. All 3 substudies will be analyzed independently of each other. Each substudy individually will consist of a screening period (up to 49 days); a double-blind treatment period (6 weeks); a safety follow-up period (30 days) for patients not rolling over into an open-label extension study; and vital status follow-up (for patients who terminated their substudy early).

Do I have to stop taking my current medications for the trial?

The trial requires that you stay on a stable dose of a cholinesterase inhibitor or memantine, if applicable. However, you cannot take certain medications prohibited by the protocol, such as anti-tau therapy or donanemab within 2 months prior to screening.

How is the drug ACP-204 different from other Alzheimer's treatments?

ACP-204 is unique because it may involve a novel approach to targeting Alzheimer's disease, potentially focusing on mechanisms related to amyloid-beta (a protein associated with Alzheimer's) and its effects on memory, which is different from existing treatments that primarily focus on symptom management. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 55 to 95 with Alzheimer's Disease Psychosis (ADP), living at home or in a facility, who have a caregiver and are stable on certain dementia medications. They must meet specific criteria for ADP diagnosis, including evidence of amyloid plaque deposition. Excluded are those needing prohibited meds, receiving end-of-life care, having conditions that explain their psychosis other than dementia, or with certain medical exclusions like atrial fibrillation.

Inclusion Criteria

I am between 55 and 95 years old and live at home or in a care facility.

I have been diagnosed with psychosis in a cognitive disorder as per IPA guidelines.

I have experienced symptoms like hallucinations or delusions for at least 2 months.

Exclusion Criteria

On a stable dose of medication?

Have been diagnosed with Alzheimer's Disease?

Are you a male or female and ≥55 and ≤95 years old?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

7 weeks

Treatment

Participants receive ACP-204 30 mg, 60 mg, or placebo once daily for 6 weeks

6 weeks

Safety Follow-up

Participants are monitored for safety after treatment if not entering the open-label extension

4 weeks

Vital Status Follow-up

Monitoring of vital status for participants who terminated their substudy early

Open-label Extension (optional)

Participants may opt into continuation of treatment long-term

Treatment Details

Interventions

• ACP-204

Trial Overview The study tests ACP-204 at two doses (30 mg and 60 mg) against a placebo in three parts: an initial phase to assess efficacy and dose response followed by two confirmatory phases for the chosen doses. Each participant undergoes screening, six weeks of treatment, safety follow-up unless entering an extension study, and vital status updates if leaving early.

Participant Groups

Group I: ACP-204 60 mg Experimental Treatment 1 Intervention

Administration once daily at approximately the same time of day, with or without food

Group II: ACP-204 30 mg Experimental Treatment 1 Intervention

Administration once daily at approximately the same time of day, with or without food

Group III: Placebo Placebo Group 1 Intervention

Administration once daily at approximately the same time of day, with or without food

Who Is Running the Clinical Trial?

ACADIA Pharmaceuticals Inc.

Lead Sponsor

Trials

49

Recruited

11,700+

Founded

1993

Headquarters

San Diego, USA

Known For

Neurological Disorders

Top Products

Nuplazid (pimavanserin), Daybue (trofinetide)

Findings from Research

ESP-102 significantly improved memory impairments in mice induced by the amyloid-β (Aβ)(1-42) peptide, as shown by behavioral tests like the passive avoidance and Morris water maze tasks, with a notable effect observed after a single dose of 100 mg/kg.

The mechanism of action for ESP-102 includes inhibition of acetylcholinesterase activity, reduction of lipid peroxidation, and attenuation of inflammatory markers in the hippocampus, suggesting it may protect against neurodegenerative changes associated with Aβ(1-42) exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-amnesic effect of ESP-102 on Aβ(1-42)-induced memory impairment in mice. Kim, DH., Jung, WY., Park, SJ., et al.[2010]

Current treatments for Alzheimer's disease primarily address symptoms rather than the underlying causes, with options like memantine and cholinesterase inhibitors available for cognitive enhancement.

Novel approaches are being explored, including repurposing existing drugs like intranasal insulin and certain antidepressants, which have shown promise in improving cognition and reducing neuropsychiatric symptoms in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease. Miziak, B., Błaszczyk, B., Czuczwar, SJ.[2021]

Site-directed antibodies targeting beta-amyloid have shown promise in transgenic mice models of Alzheimer's disease by preventing the formation of beta-amyloid and dissolving existing plaques, which helps protect against memory deficits.

Although previous human trials for active immunization with beta-amyloid were halted, new antibody preparations are now in clinical testing, supporting the idea that modulating beta-amyloid could be a viable immunotherapy approach for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-amyloidbased immunotherapy as a treatment of Alzheimers disease. Solomon, B.[2017]

In a study examining the role of amyloid P component in Alzheimer's disease, 90% of senile plaques containing beta/A4 protein also showed positive staining for amyloid P, indicating a strong association between the two.

The results suggest that amyloid P component may play a significant role in the formation of amyloid fibrils within senile plaques in the brains of individuals with Alzheimer-type dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid-P-component-like immunoreactivity in beta/A4-immunoreactive deposits in Alzheimer-type dementia brains. Kimura, M., Arai, H., Takahashi, T., et al.[2019]

In a study comparing serum amyloid P component (AP) levels, patients with Alzheimer's disease (AD) had significantly lower AP levels (22.4 µg/ml) than control subjects (34.4 µg/ml), suggesting a potential biomarker for AD.

The findings indicate that the lower AP production in AD patients may not be due to overproduction of AP in the brain, but rather a suppression of its production by the liver, challenging previous assumptions about its role in Alzheimer's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum amyloid P component level in Alzheimer's disease. Nishiyama, E., Iwamoto, N., Kimura, M., et al.[2019]

References

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

Anti-amnesic effect of ESP-102 on Aβ(1-42)-induced memory impairment in mice. [2010]

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

Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

Beta-amyloidbased immunotherapy as a treatment of Alzheimers disease. [2017]

4. Germany pubmed.ncbi.nlm.nih.gov

Amyloid-P-component-like immunoreactivity in beta/A4-immunoreactive deposits in Alzheimer-type dementia brains. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Serum amyloid P component level in Alzheimer's disease. [2019]