Alzheimer's Disease Vaccine 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 1

Recruiting

Sponsor: Institute for Molecular Medicine

Must be taking: Acetylcholine esterase inhibitors, Memantine

Must not be taking: Immunomodulatory drugs, Warfarin

Disqualifiers: Insulin-dependent diabetes, Autoimmune diseases, others

Trial Summary

What is the purpose of this trial?

Phase 1 clinical trial of AV-1959 amyloid-β vaccine for Alzheimer's disease (AD).

Do I need to stop my current medications to join the trial?

The trial requires that you stay on a stable dose of approved Alzheimer's medications for at least 3 months before starting and during the study. Other medications, like immunomodulatory drugs or certain blood thinners, must be stopped 30 days before joining.

What data supports the effectiveness of the Alzheimer's Disease Vaccine treatment for Alzheimer's Disease?

Research suggests that vaccines targeting specific proteins involved in Alzheimer's, like amyloid β, may help slow disease progression. Some studies have shown that these vaccines can generate an immune response that reduces harmful protein deposits in the brain, which is a key feature of Alzheimer's. ^{1 2 3 4 5}

Is the Alzheimer's Disease Vaccine AV-1959D safe for humans?

The AV-1959D vaccine has shown a favorable safety profile in animal studies, with no significant toxicities observed in mouse models of Alzheimer's disease, supporting its progression to human clinical trials. ^{2 3 6 7 8}

Research Team

Michael Agadjanyan, PhD

Principal Investigator

IMM

Eligibility Criteria

This trial is for men and women aged 60-85 with mild cognitive impairment due to Alzheimer's, scoring 22-30 on the MMSE and having a CDR of 0.5 or 1.0. They must have evidence of amyloid-beta in the brain via PET scan but can't join if they've had recent other treatments, immunotherapies for Alzheimer's, serious illnesses, unstable heart disease, insulin-dependent diabetes, autoimmune diseases, severe reactions to vaccines or seizures.

Inclusion Criteria

I am between 60 and 85 years old.

I have mild memory problems due to Alzheimer's, confirmed by tests and a PET scan.

Exclusion Criteria

I haven't been part of another drug study or taken any experimental drugs recently.

I haven't been hospitalized or needed serious treatment in the last 4 weeks.

I use insulin for my diabetes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AV-1959D vaccine or placebo in a randomized, double-blind manner

28 weeks

Multiple visits for immunization and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AV-1959 (Cancer Vaccine)

Trial Overview The study tests AV-1959D vaccine against a placebo in people with early Alzheimer's symptoms. It’s a Phase 1 trial designed to evaluate safety and how well participants tolerate the vaccine while monitoring any potential impact on their cognitive function over time.

Participant Groups

Group I: AV-1959D 1000 μg Active Control 1 Intervention

Group II: AV-1959D 2000 μg Active Control 1 Intervention

Group III: AV-1959D 500 μg Active Control 1 Intervention

Group IV: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Institute for Molecular Medicine

Lead Sponsor

Trials

7

Recruited

3,700+

Clinartis

Industry Sponsor

Trials

7

Recruited

270+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

Next-generation vaccines designed specifically for older adults and targeting patients with mild Alzheimer's disease show promise as a potential disease-modifying therapy, based on previous research in transgenic mouse models.

The development of these vaccines has faced many challenges over the past decade, but there is renewed optimism that they could be effective in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination against Alzheimer disease: an update on future strategies. Fettelschoss, A., Zabel, F., Bachmann, MF.[2021]

AADvac1, an active peptide vaccine targeting pathological tau in Alzheimer's disease, was found to be safe and well tolerated in a 24-month trial with 196 patients, showing lower rates of serious adverse events compared to placebo.

While AADvac1 successfully induced high levels of IgG antibodies, it did not demonstrate significant effects on cognitive and functional decline in the overall study population, indicating the need for further research to assess its clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease. Novak, P., Kovacech, B., Katina, S., et al.[2023]

The novel DNA epitope-based vaccine AV-1955 successfully generated long-term, potent anti-Aβ antibodies in rhesus macaques, indicating its potential effectiveness in targeting amyloid β for Alzheimer's disease.

AV-1955 elicited strong immune responses without targeting the body's own Aβ, suggesting a safer profile for human clinical testing compared to previous vaccines that used Aβ-specific T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques. Evans, CF., Davtyan, H., Petrushina, I., et al.[2022]

The first generation of Alzheimer disease vaccines, specifically targeting the Aβ42 peptide, showed a concerning safety issue with 6% of patients experiencing meningoencephalitis, highlighting the need for improved vaccine designs.

Next generation vaccines are focusing on targeting more specific epitopes to create a controlled immune response, aiming to balance effective immune activation without causing harmful side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active Vaccines for Alzheimer Disease Treatment. Sterner, RM., Takahashi, PY., Yu Ballard, AC.[2018]

A mucosal immunotherapy using oral and nasal administration of viral vectors effectively reduced amyloid-beta (Aβ) deposits in the brains of APP transgenic mice, suggesting a potential treatment for Alzheimer's disease.

The treatment led to increased antibody levels that inhibited Aβ aggregation in vitro, and importantly, it did not cause inflammation in any organs, indicating a safe approach for targeting Alzheimer's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mucosal immunotherapy for alzheimer's disease with viral vectors]. Hara, H., Inoue, M., Adachi, K., et al.[2010]

The study developed vaccines targeting both β-amyloid (Aβ) and tau proteins associated with Alzheimer's disease, with the AV-1959R vaccine showing the strongest immune response in mice when formulated with the Advax(CpG) adjuvant.

The dual-epitope vaccine AV-1953R induced robust antibody responses against Aβ but had lower anti-tau antibody levels compared to the single-target vaccines, suggesting that while targeting both proteins is beneficial, the immune response may vary between them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules. Davtyan, H., Zagorski, K., Rajapaksha, H., et al.[2021]

The DNA vaccine AV-1959D has shown a favorable safety profile in two different mouse models of Alzheimer's disease, with no significant toxicities observed after multiple immunizations, supporting its potential for human trials.

Biodistribution studies indicated that the vaccine remains localized at the injection site for an extended period, with no evidence of harmful effects on distant organs, which is crucial for its therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials. Petrushina, I., Hovakimyan, A., Harahap-Carrillo, IS., et al.[2022]

References

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

Vaccination against Alzheimer disease: an update on future strategies. [2021]

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

ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease. [2023]

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

Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques. [2022]

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

Active Vaccines for Alzheimer Disease Treatment. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Mucosal immunotherapy for alzheimer's disease with viral vectors]. [2010]

6. England pubmed.ncbi.nlm.nih.gov

Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules. [2021]

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

Long-Term Extensions of Randomized Vaccination Trials of ACC-001 and QS-21 in Mild to Moderate Alzheimer's Disease. [2018]

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

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials. [2022]