A Study to Assess the Effects of ACI-24.060 in Alzheimer's Disease and in Down Syndrome (ABATE Study)

NCT05462106 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: ACI-24-AD-DS-21022021-006195-172022-500069-29-00
• Study Type: interventional
• Target: 176
• Locations: 3 countries
• Sites: 19

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.

Conditions

Prodromal Alzheimer's Disease; Alzheimer's Disease; Amyloid Plaque; Beta-Amyloid; DSAD

Keywords

Dementia; Brain Diseases; Central Nervous System Diseases; Amyloid Plaque; Beta-Amyloid; Down syndrome; Immunogenicity; active immunotherapy; immune response; anti-amyloid therapy; DSAD; Alzheimer's disease

Outcome Measures

Primary Outcomes (9)

• Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related)

  From Screening to Week 74 (Study Part 1)

• Number of participants with Adverse Events (AEs) assessed by intensity (mild, moderate or severe) and causal relationship (unrelated, unlikely, possibly or probably related)

  From Screening to Week 100 (Study Part 2)

• Number of participants with abnormal MRI results

  From Baseline to Week 74 (Study Part 1)

• Number of participants with abnormal MRI results

  From Baseline to Week 100 (Study Part 2)

• Number of participants with abnormal physical and neurological examination results

  From Baseline to Week 74 (Study Part 1)

• Number of participants with abnormal physical and neurological examination results

  From Baseline to Week 100 (Study Part 2)

• Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS)

  From Baseline to Week 74 (Study Part 1)

• Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS)

  From Baseline to Week 100 (Study Part 2)

• Change from baseline in Anti-Abeta antibody titers in blood

  From Baseline to Week 100 (Study Part 2)

Secondary Outcomes (2)

• 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)

Other Outcomes (8)

• Change from baseline on brain amyloid levels

  From Baseline to W48 (Study Part 1)

• Change from baseline on tau levels

  From Baseline to W48 (Study Part 1) and to W100 (Study Part 2)

• Change from baseline in cognitive tests - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  From Baseline to Week 74 (Study Part 1)

Study Arms (9)

Placebo for Study Part 1 (Prodromal AD)

PLACEBO COMPARATOR

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

Biological: Placebo

ACI-24.060 at Dose A in Prodromal AD

EXPERIMENTAL

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

Biological: ACI-24.060 at Dose A

ACI-24.060 at Dose B in Prodromal AD

EXPERIMENTAL

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

Biological: ACI-24.060 at Dose B

ACI-24.060 at Dose C in Prodromal AD

EXPERIMENTAL

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

Biological: ACI-24.060 at Dose C

ACI-24.060 at Dose D in Prodromal AD (Optional)

EXPERIMENTAL

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

Biological: ACI-24.060 at Dose D

Placebo for Study Part 2 (Down syndrome)

PLACEBO COMPARATOR

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

Biological: Placebo

ACI-24.060 at Dose A in Down syndrome

EXPERIMENTAL

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.

Biological: ACI-24.060 at Dose A

ACI-24.060 at Dose B in Down syndrome

EXPERIMENTAL

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

Biological: ACI-24.060 at Dose B

ACI-24.060 at Dose C in Down syndrome

EXPERIMENTAL

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.

Biological: ACI-24.060 at Dose C

Interventions

ACI-24.060 at Dose B BIOLOGICAL

Administration of Dose B of ACI-24.060

ACI-24.060 at Dose B in Prodromal AD

ACI-24.060 at Dose C BIOLOGICAL

Administration of Dose C of ACI-24.060

ACI-24.060 at Dose C in Prodromal AD

ACI-24.060 at Dose D BIOLOGICAL

Administration of Dose D of ACI-24.060

ACI-24.060 at Dose D in Prodromal AD (Optional)

Placebo BIOLOGICAL

Administration of Placebo

Placebo for Study Part 1 (Prodromal AD)

ACI-24.060 at Dose A BIOLOGICAL

Administration of Dose A of ACI-24.060

ACI-24.060 at Dose A in Prodromal AD

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0.5.
• 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 21.
• PET scan at screening consistent with the presence of amyloid pathology.
• Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.
• Subjects must have a study partner who has direct and regular contact, at least 10 hours per week, with the subject and who is able to provide reliable answers to questions related to the subject, according to the study investigator.

You may not qualify if:

• 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.
• MRI scan at screening showing a single area of cerebral vasogenic edema, superficial siderosis, or evidence of a previous macro-hemorrhage or showing more than 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite"). Evidence of space occupying lesions other than benign meningioma of less than 1 cm diameter, more than 2 lacunar infarcts, or 1 single infarct larger than 1 cm in diameter. Screening MRI scan showing structural evidence of alternative pathology not consistent with AD and is considered to be at the origin of subject's symptoms.
• Deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, judged to be clinically significant by the investigator.
• Subjects with a positive Human Immunodeficiency Virus (HIV-1 and 2) test at screening.
• Subjects with clinical or laboratory evidence of active hepatitis B or C at screening (eg, HBV or HCV antigens).
• Subjects with positive syphilis serology consistent with active syphilis at screening.

Sponsors & Collaborators

• AC Immune SA: lead
• Worldwide Clinical Trials: collaborator

Study Sites (19)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

RECRUITING

Indiana University / IU Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Medical Center Research Institute

Fairway, Kansas, 66205-2513, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

The Washington University

St Louis, Missouri, 63130, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2103, United States

RECRUITING

UT Health San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Fundació ACE, Institut Català de Neurociències Aplicades

Barcelona, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Hospital Universitario Virgen De Las Nieves

Granada, Spain

WITHDRAWN

Hospital Clínico San Carlos

Madrid, Spain

RECRUITING

Hospital Universitario de la Princesa

Madrid, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Spain

RECRUITING

Cambridge and Peterborough NHS Foundation Trust - Windsor Research Units

Cambridge, United Kingdom

RECRUITING

Liverpool University Hospitals NHS Foundation Trust

Liverpool, United Kingdom

RECRUITING

Re:Cognition Health Limited

London, United Kingdom

RECRUITING

South London and Maudsley NHS Foundation Trust of The Maudsley Hospital

London, United Kingdom

RECRUITING

Oxford Health NHS Foundation Trust

Oxford, United Kingdom

RECRUITING

MeSH Terms

Conditions

Plaque, Amyloid; Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Down Syndrome

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Michael Rafii, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivier Sol, MD

CONTACT

+41 21 345 9121; clinicaltrials@acimmune.com

Benedicte Le

CONTACT

+41 21 345 9121; clinicaltrials@acimmune.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 18, 2022
• Study Start: June 21, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

GB (5); ES (7); US (7)