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

Trial Summary

What is the purpose of this trial?

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 disease and in non-demented adults with Down syndrome.

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.

What data supports the effectiveness of the drug ACI-24.060 for Alzheimer's Disease and Down Syndrome?

The research highlights the importance of identifying and tracking symptoms and biomarkers (biological indicators) for Alzheimer's in people with Down syndrome, which can help in assessing treatment effectiveness. While specific data on ACI-24.060 is not provided, understanding these biomarkers and symptoms is crucial for evaluating any new drug's impact. ^{1 2 3 4 5}

How is the drug ACI-24.060 unique for treating Alzheimer's disease in Down syndrome?

ACI-24.060 is unique because it targets amyloid beta (Aβ) pathology, which is a key factor in Alzheimer's disease development in individuals with Down syndrome. This approach is novel as there are currently no pharmacological treatments available specifically for Alzheimer's disease in Down syndrome, making ACI-24.060 a potentially groundbreaking option. ^{1 5 6 7 8}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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) 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]

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]

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]

References

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

Down syndrome and Alzheimer's disease: Common pathways, common goals. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study. [2021]

3. Germany 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Integrating Biomarker Outcomes into Clinical Trials for Alzheimer's Disease in Down Syndrome. [2023]

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

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

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

Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2022]