ABATE

Information about the drug that will be tested in the study

Administration

Participants with prodromal Alzheimer's disease will receive injections of the vaccine (ACI-24.060) or placebo at predefined time points over 48 weeks.

Participants with Down syndrome will receive injections of ACI-24.060 or placebo at predefined time points over 74 weeks.

Is the drug already on the market for another medical condition?

No

Will all participants receive the same drug?

Participants with prodromal Alzheimer's disease and participants with Down syndrome will be randomly assigned to one of the two groups receiving injections of either:

• the vaccine ACI-24.060
• or  placebo (also called a dummy treatment which is an inactive substance identical in appearance to the drug being tested with no active therapeutic effect).

The probability to receive either ACI-24.060 or placebo is predefined in the study protocol and is also mentioned in the informed consent form.

Neither the participant nor his/her doctor will know if the person is receiving the investigational drug or the placebo.

Information about participating in the trial

What are the researchers trying to find out?

The purpose of the study is to evaluate the safety, tolerability and immunogenicity (capability of the vaccine to generate antibodies in participants) and pharmacodynamic effects (the properties of the biological effect generated by the vaccine in participants) of ACI-24.060 in people with prodromal Alzheimer's disease and in people with Down syndrome.

How long will the treatment last?

48 weeks for participants with prodromal Alzheimer's disease (Study part 1)

74 weeks for participants with Down syndrome (Study part 2)

After the completion of the treatment period, the participants will be followed in the study, respectively up to week 74 in people with prodromal Alzheimer's disease, and up to week 100 in people with Down syndrome.

What your involvement will entail?

During the study, participants will be asked:

• To complete a test that will assess their suicidal ideation behaviour (this is a test called C-SSRS)
• To complete some laboratory/biological tests (i.e. blood tests) to evaluate the emergent adverse effects (unfavourable signs, symptoms or diseases temporally associated with the use of the drug tested in the study
• To complete other tests that will assess their functioning, cognition and memory related to the study part participants are taking part (i.e. tests like CDR, RBANS, ADAS-Cog 13, mCRT, CANTAB-PAL)
• Participants will be asked to undertake brain scans (PET, MRI).

Further information on the procedures, tests and number of visits can be obtained from the study team.

Who can participate in this study?

Who can participate in the study?

To take part in the study Part 1, participants with prodomal Alzheimer's disease must (main inclusion criteria):

• Be between 50 and 85 years old
• Have evidence of abnormal accumulation of amyloid in their brain (PET scan)
• Have a score of 0.5 in the Clinical Dementia Rating-Global Score (CDR). This would suggest that the person has an impairment in its memory that is at a mild stage
• If the person is taking approved symptomatic medication for dementia (i.e. donepezil, rivastigmine, galantamine or memantine) the dosing regimen must have been stable for at least 2 months prior to the baseline visit.

To take part in the study Part 2, participants with Down syndrome must (main inclusion criteria):

• Be 35 to 50 years old. Participants between 35 and 39 years old may be considered on the condition that there is amyloid evidence (at PET and/or in body fluids) compatible with Alzheimer’s disease pathology
• Have a cytogenetic diagnosis of Down syndrome (trisomy 21 or complete unbalanced translocation of the chromosome 21)
• Have mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.

All participants must have a study partner who has direct and regular contact, at least 10 hours per week, with the participant and who is able to provide reliable answers to questions related to the participant, according to the study investigator.

Who cannot participate in the study?

People cannot take part in the study if they have or have experienced (main exclusion criteria):

• A medical condition that may interfere with the safety and/or efficacy of the study vaccine (e.g. moderate and/or severe untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions)
• History of brain diseases including neurological disorders. A more detailed list can be obtained from the study team
• Any alcohol or drug abuse or dependence within the past 5 years
• Concomitant or past history psychiatric or neurologic disorder other than those considered to be related to Alzheimer’s disease (e.g. head injury with loss of consciousness, symptomatic stroke, Parkinson's disease, severe carotid occlusive disease, transient ischemic attacks hemorrhagic and/or non-hemorrhagic stroke)
• Significant risk of suicide
• Positive HIV test or Active hepatitis B and/or C
• Ongoing treatment with any approved anti-amyloid passive immunotherapy for Alzheimer’s disease
• Previous treatment with ACI-24 or any other active immunotherapy against Alzheimer’s disease
• Previous treatment with any investigantional and/or marketed passive immunotherapy againt Alzheimer's disease within 6 months before study participation
• Use of symptomatic treatments of Alzheimer’s disease (e.g. acetylcholinesterase inhibitors) or glutamatergic drugs if not on stable dose for at least 2 months before screening.

Additional main exclusion criteria for people with Down syndrome (study part 2):

• Clinical diagnosis of Alzheimer's disease dementia in Down syndrome as per International Classification of Diseases 10 (ICD-10)

Information for your doctor

EudraCT Number

2021-006195-17

Clinicaltrials.gov identifier

NCT05462106

Study contact information

clinicaltrials@acimmune.com

+41 21 345 9121

Link to full text

https://clinicaltrials.gov/ct2/show/NCT05462106

The information contained in this document is based on information available on public registries (e.g. clinicaltrials.gov website) in August 2023.

The pharmaceutical company running this trial has reviewed this document.