ACI-24.060 for Alzheimer's Disease and Down Syndrome

Recruiting at 18 trial locations

Overseen By Benedicte Le

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AC Immune SA

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Antidepressants, Typical antipsychotics, Opioids, Immunosuppressants

Disqualifiers: Unstable medical condition, Drug abuse, Seizures, others

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks for Study Part 1 and 74 weeks for Study Part 2

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a treatment called ACI-24.060 for individuals with early-stage Alzheimer's disease and adults with Down syndrome who do not have dementia. The trial explores different doses of ACI-24.060 to assess its efficacy and the body's response. Suitable participants include those showing early signs of Alzheimer's or adults with Down syndrome, particularly if they have mild intellectual disabilities and a supportive person to assist them during the trial. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that participants either not take any Alzheimer's medications or be on a stable dose of certain Alzheimer's drugs (like acetylcholinesterase inhibitors or memantine) for at least 2 months before starting. Some medications, like certain antidepressants, antipsychotics, and immunosuppressants, may need to be stopped or adjusted, so it's best to discuss your specific medications with the study team.

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

Research has shown that ACI-24.060 is generally safe and well-tolerated. In studies involving individuals with Down syndrome, no serious negative reactions to the drug occurred, indicating that participants did not experience severe side effects from the treatment. Ongoing research aims to confirm these results and determine if ACI-24.060 can alleviate Alzheimer's disease symptoms in various groups, including those with Down syndrome. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ACI-24.060 because it offers a novel approach to tackling Alzheimer's disease and Down syndrome. Unlike most treatments that mainly focus on symptom management, ACI-24.060 targets amyloid plaques in the brain, which are believed to play a key role in these conditions. This innovative mechanism could potentially alter the disease's progression rather than just alleviating symptoms. Moreover, ACI-24.060 is being tested for both Alzheimer's and Down syndrome, which is unique since many therapies don't address the overlap between these conditions. This dual application broadens its potential impact and highlights its versatility as a treatment option.

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

Research has shown that ACI-24.060, a vaccine, is being tested in this trial to assist people with early signs of Alzheimer's disease and adults with Down syndrome. Participants will receive different doses of ACI-24.060 or a placebo, based on their assigned treatment arm. Early clinical data indicate that ACI-24.060 is generally safe and well-tolerated. This treatment targets and reduces brain amyloid, a protein linked to Alzheimer's. In studies involving both Alzheimer's and Down syndrome, the body responded to the drug as expected. While more research is needed, these findings suggest that ACI-24.060 could be promising for slowing or managing symptoms in these conditions. ^{1 2 5 6 7}

Who Is on the Research Team?

Michael Rafii, MD

Principal Investigator

University of Southern California, Alzheimer's Therapeutic Research Institute, 9860 Mesa Rim Rd, San Diego, CA 92121, USA

Are You a Good Fit for This Trial?

This trial is for adults aged 50-75 with early-stage Alzheimer's (prodromal AD) and a specific type of dementia score, or non-demented adults aged 35-50 with Down syndrome. Participants must have evidence of amyloid brain plaques and can be on stable Alzheimer's medications.

Inclusion Criteria

Study Part 1: Clinical Dementia Rating (CDR)-Global Score of 0.5

Study Part 1: PET scan at screening consistent with the presence of amyloid pathology

I have Down syndrome with a confirmed genetic diagnosis.

Exclusion Criteria

Subjects with positive syphilis serology consistent with active syphilis at screening

I do not have any health conditions that could affect the study's safety or results.

I am not taking any medications that are excluded in this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACI-24.060 or placebo at predefined time points

48 weeks for Study Part 1 and 74 weeks for Study Part 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Optional Extension

Participants may optionally receive additional doses of ACI-24.060

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ACI-24.060

Trial Overview The study tests various doses of ACI-24.060 against a placebo to evaluate its safety, how well it's tolerated, the immune response it generates, and its effects on brain plaque in those with prodromal Alzheimer’s Disease and adults with Down Syndrome.

How Is the Trial Designed?

Group I: ACI-24.060 at Dose Y (Optional) Experimental Treatment 1 Intervention

Participants with Down syndrome may optionally receive a dose Y of ACI-24.060 at predefined time points over 74 weeks.

Group II: ACI-24.060 at Dose X Experimental Treatment 1 Intervention

Participants with Down syndrome receive dose X of ACI-24.060 at predefined time points over 74 weeks. Dose X will be a dose already tested in Study Part 1.

Group III: ACI-24.060 at Dose D (Optional) Experimental Treatment 1 Intervention

Prodromal AD participants receive dose D of ACI-24.060 at predefined time points over 48 weeks. This arm is optional.

Group IV: ACI-24.060 at Dose C (Optional) Experimental Treatment 1 Intervention

Prodromal AD participants receive dose C of ACI-24.060 at predefined time points over 48 weeks. This arm is optional.

Group V: ACI-24.060 at Dose B (Optional) Experimental Treatment 1 Intervention

Prodromal AD participants receive dose B of ACI-24.060 at predefined time points over 48 weeks. This arm is optional.

Group VI: ACI-24.060 at Dose A Experimental Treatment 1 Intervention

Prodromal AD participants receive dose A of ACI-24.060 at predefined time points over 48 weeks

Group VII: Placebo for Study Part 2 (Down syndrome) Placebo Group 1 Intervention

Participants with Down syndrome receive placebo at predefined time points over 74 weeks

Group VIII: Placebo for Study Part 1 (Prodromal AD) Placebo Group 1 Intervention

Prodromal AD participants receive placebo at predefined time points over 48 weeks

Who Is Running the Clinical Trial?

AC Immune SA

Lead Sponsor

Trials

9

Recruited

480+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

Individuals with Down syndrome (DS) are at a high risk of developing Alzheimer's disease (AD), with nearly all showing AD pathology by their 30s and about 70% developing dementia by age 55-60.

A recent workshop identified key research priorities to address this issue, including drug development, clinical staging, cognitive assessment, and fostering collaborations to create effective treatments for AD in individuals with DS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Down syndrome and Alzheimer's disease: Common pathways, common goals. Hartley, D., Blumenthal, T., Carrillo, M., et al.[2022]

In a study of 310 adults with Down syndrome and Alzheimer's disease, those treated with cholinesterase inhibitors had a significantly longer median survival time of 5.59 years compared to 3.45 years for those not on medication, indicating the potential efficacy of these drugs.

The use of cholinesterase inhibitors also showed early benefits in maintaining cognitive function, suggesting that these medications could be valuable for improving quality of life in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study. Eady, N., Sheehan, R., Rantell, K., et al.[2021]

The Alzheimer's Biomarker Consortium Down Syndrome (ABC-DS) and the European Horizon 21 Consortium are gathering important data on Alzheimer's Disease biomarkers in adults with Down syndrome, who are genetically at higher risk for developing the disease.

The findings from these studies will help identify the most relevant biomarkers for clinical trials, and the Alzheimer's Clinical Trial Consortium - Down syndrome (ACTC-DS) aims to facilitate international clinical trials using this data to improve outcomes for individuals with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Biomarker Outcomes into Clinical Trials for Alzheimer's Disease in Down Syndrome. Rafii, MS., Zaman, S., Handen, BL.[2023]

Adults with Down syndrome have a significantly higher risk of developing Alzheimer's disease, with most showing signs of dementia by their late 60s, primarily due to the overexpression of the amyloid precursor protein gene on chromosome 21.

A multicenter longitudinal study funded by NIA/NICHD is currently investigating biomarkers of Alzheimer's disease in adults with Down syndrome, aiming to enhance our understanding of the disease in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Search for Biomarkers of Alzheimer's Disease in Down Syndrome. Handen, BL.[2023]

Individuals with Down syndrome (DS) are at high risk for developing Alzheimer's disease (AD) by their 30s and often show signs of dementia by age 60, highlighting the urgent need for effective treatments.

Recent studies using the Ts65Dn mouse model of DS have shown that various drugs can improve learning and memory deficits, suggesting that pharmacological interventions may help mitigate cognitive decline in people with DS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Gardiner, KJ.[2018]

Individuals with Down syndrome (DS) show elevated levels of amyloid β (Aβ) pathology, similar to those with Alzheimer's disease, indicating a potential link between Aβ accumulation and cognitive decline in DS.

The antibody lecanemab (BAN2401) demonstrated promising results in detecting Aβ deposits in DS and is currently being tested in a phase 3 clinical trial, suggesting it may help preserve cognitive function in individuals with DS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease. Johannesson, M., Sahlin, C., Söderberg, L., et al.[2021]

In a study of 412 adults with Down syndrome, approximately 20% of those aged 40 and under, 40% aged 41-50, and 45% aged 51 and over showed signs of acquired mild cognitive impairment (AMCI), indicating a significant risk for early onset Alzheimer's disease.

The research suggests that a single point assessment can effectively identify AMCI in adults with Down syndrome, and the prevalence data indicates that the risk of developing Alzheimer's may be influenced by additional factors, such as ApoE status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired mild cognitive impairment in adults with Down syndrome: Age-related prevalence derived from single point assessment data normed by degree of intellectual disability. Oliver, C., Adams, D., Holland, AJ., et al.[2022]

A new comprehensive symptom menu was developed to help track Alzheimer's disease progression in adults with Down syndrome, incorporating input from both clinicians and caregivers to ensure clarity and relevance.

The final menu includes 58 goal areas with a total of 623 descriptors, enhancing the ability to monitor symptoms and treatment effectiveness in this population, which is crucial as life expectancy increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a symptom menu to facilitate Goal Attainment Scaling in adults with Down syndrome-associated Alzheimer's disease: a qualitative study to identify meaningful symptoms. Knox, K., Stanley, J., Hendrix, JA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05462106

A Study to Assess the Effects of ACI-24.060 in Alzheimer's ... The purpose of this study is to assess the safety, tolerability, immunogenicity and pharmacodynamic effects of ACI-24.060 in subjects with prodromal Alzheimer's ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12173829/

Current advances and unmet needs in Alzheimer's disease ... The study aims to assess the safety, tolerability, and immunogenicity of ACI‐24.060, with a focus on its potential to reduce brain amyloid ...

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.075830

4. An innovative clinical trial designed to evaluate the effects ... ACI-24 is a liposomal vaccine targeting Abeta. Initial clinical data demonstrated safety and pharmacodynamic response, both in sporadic AD and people with DS.

4. ir.acimmune.com ir.acimmune.com/news-releases/news-release-details/ac-immune-reports-interim-safety-data-phase-1b2-abate-trial-aci

AC Immune Reports Interim Safety Data from Phase 1b/2 ... ACI-24.060 has received Fast Track designation from the U.S. FDA for the treatment of AD. The Company previously reported positive interim ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-aci-24-060-for-patients-with-early-alzheimers-disease-and-adults-with-down-syndrome/

Study on the Safety and Effects of ACI-24.060 for Patients ... ACI-24.060 is a medication being studied for its potential to help people with early signs of Alzheimer's disease and adults with Down syndrome.

6. globenewswire.com globenewswire.com/news-release/2024/12/10/2994352/0/en/AC-Immune-Reports-Interim-Safety-Data-from-Phase-1b-2-ABATE-Trial-of-ACI-24-060-in-Down-syndrome.html

AC Immune Reports Interim Safety Data from Phase 1b/2 ... ACI-24.060 was generally safe and well tolerated in individuals with Down syndrome with no serious adverse events related to the study drug · No ...

7. abate-study.com abate-study.com/

ABATE study | The ABATE study is an important step in testing ACI-24.060's safety and showing whether it can slow down Alzheimer's disease in people with Down syndrome.