Alzheimer's Disease Vaccine for Alzheimer's Disease

Not currently recruiting at 6 trial locations

Overseen By Anahit Ghochikyan, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new vaccine, AV-1959, which targets Alzheimer's disease. Researchers seek to determine if the vaccine can slow down or improve symptoms in individuals with mild cognitive impairment or mild dementia due to Alzheimer's. The trial will include different groups: some will receive the vaccine at varying doses, while others will receive a placebo (a non-active substance for comparison). Suitable candidates have mild memory problems due to Alzheimer's and are already on stable medication for it.

As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the AV-1959D vaccine for Alzheimer's disease has been safe in early animal studies. Tests in two different types of mice with Alzheimer's disease showed that the vaccine was well-tolerated, with no major safety issues. As this trial is in an early stage, it primarily focuses on safety. Participation will provide important information about how the vaccine affects people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Alzheimer's disease focus on managing symptoms with medications like cholinesterase inhibitors and memantine. However, AV-1959D is unique because it's a vaccine that aims to prevent or slow down the disease by targeting beta-amyloid plaques, a hallmark of Alzheimer's. This new approach could potentially modify the disease process itself, rather than just alleviating symptoms. Researchers are excited about AV-1959D because, if successful, it could offer a more proactive way to tackle Alzheimer's, potentially reducing the disease's progression from the onset.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research has shown that the AV-1959D vaccine could be promising for treating Alzheimer's disease. Animal studies indicate that it can prevent the buildup of beta-amyloid, a protein linked to Alzheimer's. This buildup is believed to cause brain cell death, so stopping it might help protect the brain. Early tests on older adults suggest the vaccine triggers a strong immune response against beta-amyloid. Animal studies have also shown it to be safe, with no major side effects reported. These findings suggest AV-1959D might help slow or stop the progression of Alzheimer's. Participants in this trial will receive different dosages of AV-1959D or a placebo to further evaluate its effectiveness and safety. ^{4 5 6 7 8}

Who Is on the Research Team?

Michael Agadjanyan, PhD

Principal Investigator

IMM

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AV-1959

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.

How Is the Trial Designed?

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

Group II: AV-1959D 1000 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+

Published Research Related to This Trial

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]

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]

ACC-001 (vanutide cridificar), an anti-amyloid-beta vaccine, was well tolerated in subjects with mild to moderate Alzheimer's disease across multiple countries, with no new safety concerns identified during long-term treatment.

The vaccine effectively elicited anti-amyloid antibody responses, with the highest antibody levels observed in participants receiving ACC-001 combined with the QS-21 adjuvant, indicating its potential for long-term immunotherapy in Alzheimer's disease.

NCBI (Pubmed)

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. Hull, M., Sadowsky, C., Arai, H., et al.[2018]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05642429?intr=AV-1959D&rank=1

Study of AV-1959D, an Amyloid Beta Vaccine A Phase I, Randomized, Double-Blind Study to Evaluate Safety and Tolerability of Amyloid-β Vaccine, AV-1959D , in Patients With Early Alzheimer's Disease.

2. withpower.com withpower.com/trial/phase-1-alzheimer-disease-11-2022-97891

Alzheimer's Disease Vaccine for Alzheimer's Disease 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, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8772258/

Characterization and preclinical evaluation of the cGMP grade ... These data suggest that our AV-1959D vaccine can rapidly induce a robust anti-Aβ antibody production in vaccinated elderly individuals with pre-existing memory ...

4. nia.nih.gov nia.nih.gov/2021-2022-alzheimers-disease-related-dementias-scientific-advances/drug-development

Alzheimer's & Related Dementias: Drug Development Studies in animal models have shown that AV-1959D is safe and effective at preventing beta-amyloid accumulation and brain cell death. As a ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/biovie-report-win-parkinsons-alzheimers-candidate/

BioVie report another win with Alzheimer's and Parkinson's ... The data showed that NE3107 patients experienced a significant improvement of -2.4 points for the sleep/fatigue domain of the non-motor symptom ...

6. synapse.patsnap.com synapse.patsnap.com/drug/5bb28ea7d9c94c17a52b1d4d4ae53d80

AV-1959D - Drug Targets, Indications, Patents Taken together, the safety data from two different mouse models of AD substantiate a favorable safety profile of the cGMP grade AV-1959D vaccine ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32119976/

Characterization and Preclinical Evaluation of the cGMP ... Taken together, the safety data from two different mouse models of AD substantiate a favorable safety profile of the cGMP grade AV-1959D vaccine supporting its ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05642429/study-of-av-1959d-an-amyloid-beta-vaccine

Study of AV-1959D, an Amyloid Beta Vaccine Study Summary. Phase 1 clinical trial of AV-1959 amyloid-β vaccine for Alzheimer's disease (AD).