A Phase 1b/2, Multicenter, Adaptive, Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Immunogenicity, and Pharmacodynamic Effects of ACI-24.060 in Subjects With Prodromal Alzheimer's Disease and in Adults With Down Syndrome (ABATE)
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Not specified
- Sponsor
- AC Immune SA
- Enrollment
- 176
- Locations
- 19
- Primary Endpoint
- Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Detailed Description
This phase 1b/2 study will be in 2 parts. Study Part 1 will involve subjects with prodromal Alzheimer's disease. Study Part 2 will involve subjects with Down syndrome.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Study Part 1
- •Age ≥50 and ≤85 years at screening.
- •Diagnosis of prodromal AD: MCI due to AD according to National Institute on Aging Alzheimer's Association (NIA-AA) criteria.
- •PET scan at screening consistent with the presence of amyloid pathology.
- •Clinical Dementia Rating (CDR)-Global Score of 0.
- •Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor (ACHEI) and/or memantine for at least 2 months prior to baseline.
- •Study Part 2
- •Age ≥35 and ≤50 years at screening (subjects with DS with age ≥35 and ≤39 years may be considered on the condition that there is prior evidence of amyloid results compatible with AD pathology at PET-scan and/or in biofluids).
- •Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome
- •PET scan at screening consistent with the presence of amyloid pathology.
Exclusion Criteria
- •Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study treatment (eg, 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), as per investigator's judgement.
- •DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years.
- •History or presence of uncontrolled seizures. If history of seizures, they must be well controlled with no occurrence of seizures in the 2 years before study screening. The use of antiepileptic medications is permitted.
- •Concomitant or past history psychiatric or neurologic disorder other than those considered to be related to AD (eg, head injury with loss of consciousness, symptomatic stroke, Parkinson's disease, severe carotid occlusive disease, transient ischemic attacks \[TIAs\], hemorrhagic and/or non-hemorrhagic stroke).
- •History of meningitis or meningoencephalitis.
- •History of moderate or severe traumatic brain injury.
- •History of or presence of inflammatory neurological disorders.
- •History or presence of immunological or autoimmune disorders.
- •History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe allergic reaction to previous vaccines, foods, and/or medications.
- •Significant risk of suicide, defined using the C-SSRS as the subject answering "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behavior within the past 12 months.
Arms & Interventions
Placebo for Study Part 1 (Prodromal AD)
Prodromal AD participants receive placebo at predefined time points over 48 weeks
Intervention: Placebo
ACI-24.060 at Dose A in Prodromal AD
Prodromal AD participants receive dose A of ACI-24.060 at predefined time points over 48 weeks
Intervention: ACI-24.060 at Dose A
ACI-24.060 at Dose B in Prodromal AD
Prodromal AD participants receive dose B of ACI-24.060 at predefined time points over 48 weeks.
Intervention: ACI-24.060 at Dose B
ACI-24.060 at Dose C in Prodromal AD
Prodromal AD participants receive dose C of ACI-24.060 at predefined time points over 48 weeks.
Intervention: ACI-24.060 at Dose C
ACI-24.060 at Dose D in Prodromal AD (Optional)
Prodromal AD participants receive dose D of ACI-24.060 at predefined time points over 48 weeks. This arm is optional.
Intervention: ACI-24.060 at Dose D
Placebo for Study Part 2 (Down syndrome)
Participants with Down syndrome receive placebo at predefined time points over 74 weeks
Intervention: Placebo
ACI-24.060 at Dose A in Down syndrome
Participants with Down syndrome receive dose A of ACI-24.060 at predefined time points over 74 weeks. Dose A will be a dose already tested in Study Part 1.
Intervention: ACI-24.060 at Dose A
ACI-24.060 at Dose B in Down syndrome
Participants with Down syndrome may optionally receive a dose B of ACI-24.060 at predefined time points over 74 weeks.
Intervention: ACI-24.060 at Dose B
ACI-24.060 at Dose C in Down syndrome
Participants with Down syndrome receive dose C of ACI-24.060 at predefined time points over 74 weeks. Dose C will be a dose already tested in Study Part 1.
Intervention: ACI-24.060 at Dose C
Outcomes
Primary Outcomes
Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related)
Time Frame: From Screening to Week 100 (Study Part 2)
Number of participants with abnormal MRI results
Time Frame: From Baseline to Week 100 (Study Part 2)
Change from baseline in Anti-Abeta antibody titers in blood
Time Frame: From Baseline to Week 100 (Study Part 2)
Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: From Baseline to Week 100 (Study Part 2)
Number of participants with abnormal physical and neurological examination results
Time Frame: From Baseline to Week 100 (Study Part 2)
Secondary Outcomes
- Change from baseline in Anti-Abeta antibody titers(From Baseline to Week 74 (Study Part 1))
- Change from baseline on brain amyloid levels(From Baseline to W100 (Study Part 2))