RECRUITING

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

Conditions

Alzheimer's Disease Prodromal Alzheimer's Disease Amyloid Plaque Beta-Amyloid Alzheimer's Disease in Down Syndrome Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Down syndrome Vaccine Immunogenicity

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2022-06-21

Study Completion:2026-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05462106

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:35 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥50 and ≤85 years at screening. 2. Diagnosis of prodromal AD: MCI due to AD according to National Institute on Aging Alzheimer's Association (NIA-AA) criteria. 3. PET scan at screening consistent with the presence of amyloid pathology. 4. Clinical Dementia Rating (CDR)-Global Score of 0.5. 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. 1. 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). 2. Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21. 3. PET scan at screening consistent with the presence of amyloid pathology. 4. Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification. 5. 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.	1. Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study vaccine (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. 2. DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years. 3. 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. 4. 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). 5. History of meningitis or meningoencephalitis. 6. History of moderate or severe traumatic brain injury. 7. History of inflammatory neurological disorders. 8. History or presence of immunological or inflammatory conditions, including neurological disorders, judged to be clinically significant by the investigator. 9. History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe allergic reaction to previous vaccines, foods, and/or medications. 10. 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. 11. 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. 12. Deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, judged to be clinically significant by the investigator. 13. Subjects with a positive Human Immunodeficiency Virus (HIV-1 and 2) test at screening. 14. Subjects with clinical or laboratory evidence of active hepatitis B or C at screening (eg, HBV or HCV antigens). 15. Subjects with positive syphilis serology consistent with active syphilis at screening. 16. MRI examination cannot be done for any reason, including but not limited to metal implants contraindicated for MRI and/or severe claustrophobia. 17. Any contraindication for PET scan imaging. 18. Any contraindication to lumbar puncture in subjects undergoing this procedure (note: lumbar puncture is optional in subjects with DS). 19. Previous treatment with ACI-24 or any other active immunotherapy against AD at any time in the past unless there is firm evidence that the subject received placebo only and the placebo formulation is not expected to induce any specific immune response. 20. Previous treatment with any investigational and/or marketed passive immunotherapy against AD within 6 months before screening or 5 half-lives, whichever is longer, unless there is firm evidence that the subject received placebo only. 21. Ongoing treatment with any approved anti-amyloid passive immunotherapy for Alzheimer's disease. 22. Use of acetylcholinesterase inhibitor or glutamatergic drugs (eg, memantine, topiramate, lamotrigine) if not on stable dose for at least 2 months before screening. 23. Any vaccine received within the 2 weeks before screening, including an anti-influenza or anti-COVID 19 vaccine received within 4 weeks before randomization. 24. Subjects with treated hypothyroidism not on a stable dose of replacement medication for at least 2 months before screening and having clinically significant abnormal serum T4 and/or thyroid stimulating hormone at screening. 25. Subjects undergoing lumbar puncture and being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower. 26. Use of antidepressants (other than selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors at stable dose); typical antipsychotics; γ-aminobutyric acid agonists (eg, gabapentin); or stimulants (eg, methylphenidate, modafinil). Stable doses of atypical antipsychotics or benzodiazepines are only allowed if this is not considered to influence the safety and the efficacy of the study vaccine according to the site investigator and the sponsor medical monitor. 27. Chronic use of opioid analgesics. A limited treatment duration for acute conditions until 24 hours before cognitive assessment is allowed. 28. Current use of immunosuppressant or immunomodulating drugs or their use within the 6 months before study screening. Current use of oral steroids or their use within the 3 months before study screening. 29. Clinical diagnosis of AD dementia in DS as per International Classification of Diseases 10 (ICD-10). 30. DSQIID \>20. 31. Intelligence quotient score \<40 (KBIT-2).

Inclusion Criteria

Exclusion Criteria

1. Age ≥50 and ≤85 years at screening.
2. Diagnosis of prodromal AD: MCI due to AD according to National Institute on Aging Alzheimer's Association (NIA-AA) criteria.
3. PET scan at screening consistent with the presence of amyloid pathology.
4. Clinical Dementia Rating (CDR)-Global Score of 0.5.
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.
1. 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).
2. Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21.
3. PET scan at screening consistent with the presence of amyloid pathology.
4. Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.
5. 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.

1. Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study vaccine (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.
2. DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years.
3. 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.
4. 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).
5. History of meningitis or meningoencephalitis.
6. History of moderate or severe traumatic brain injury.
7. History of inflammatory neurological disorders.
8. History or presence of immunological or inflammatory conditions, including neurological disorders, judged to be clinically significant by the investigator.
9. History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe allergic reaction to previous vaccines, foods, and/or medications.
10. 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.
11. 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.
12. Deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, judged to be clinically significant by the investigator.
13. Subjects with a positive Human Immunodeficiency Virus (HIV-1 and 2) test at screening.
14. Subjects with clinical or laboratory evidence of active hepatitis B or C at screening (eg, HBV or HCV antigens).
15. Subjects with positive syphilis serology consistent with active syphilis at screening.
16. MRI examination cannot be done for any reason, including but not limited to metal implants contraindicated for MRI and/or severe claustrophobia.
17. Any contraindication for PET scan imaging.
18. Any contraindication to lumbar puncture in subjects undergoing this procedure (note: lumbar puncture is optional in subjects with DS).
19. Previous treatment with ACI-24 or any other active immunotherapy against AD at any time in the past unless there is firm evidence that the subject received placebo only and the placebo formulation is not expected to induce any specific immune response.
20. Previous treatment with any investigational and/or marketed passive immunotherapy against AD within 6 months before screening or 5 half-lives, whichever is longer, unless there is firm evidence that the subject received placebo only.
21. Ongoing treatment with any approved anti-amyloid passive immunotherapy for Alzheimer's disease.
22. Use of acetylcholinesterase inhibitor or glutamatergic drugs (eg, memantine, topiramate, lamotrigine) if not on stable dose for at least 2 months before screening.
23. Any vaccine received within the 2 weeks before screening, including an anti-influenza or anti-COVID 19 vaccine received within 4 weeks before randomization.
24. Subjects with treated hypothyroidism not on a stable dose of replacement medication for at least 2 months before screening and having clinically significant abnormal serum T4 and/or thyroid stimulating hormone at screening.
25. Subjects undergoing lumbar puncture and being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower.
26. Use of antidepressants (other than selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors at stable dose); typical antipsychotics; γ-aminobutyric acid agonists (eg, gabapentin); or stimulants (eg, methylphenidate, modafinil). Stable doses of atypical antipsychotics or benzodiazepines are only allowed if this is not considered to influence the safety and the efficacy of the study vaccine according to the site investigator and the sponsor medical monitor.
27. Chronic use of opioid analgesics. A limited treatment duration for acute conditions until 24 hours before cognitive assessment is allowed.
28. Current use of immunosuppressant or immunomodulating drugs or their use within the 6 months before study screening. Current use of oral steroids or their use within the 3 months before study screening.
29. Clinical diagnosis of AD dementia in DS as per International Classification of Diseases 10 (ICD-10).
30. DSQIID \>20.
31. Intelligence quotient score \<40 (KBIT-2).

Contacts and Locations

Study Contact

Olivier Sol, MD

CONTACT

+41 21 345 9121

clinicaltrials@acimmune.com

Benedicte Le

CONTACT

+41 21 345 9121

clinicaltrials@acimmune.com

Principal Investigator

Michael Rafii, MD

PRINCIPAL_INVESTIGATOR

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

Study Locations (Sites)

Barrow Neurological Institute

Phoenix, Arizona, 85013

United States

Indiana University / IU Health

Indianapolis, Indiana, 46202

United States

University of Kansas Medical Center Research Institute

Fairway, Kansas, 66205-2513

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

The Washington University

Saint Louis, Missouri, 63130

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2103

United States

UT Health San Antonio

San Antonio, Texas, 78229

United States

Collaborators and Investigators

Sponsor: AC Immune SA

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-21

Study Completion Date2026-06

Study Record Updates

Study Start Date2022-06-21

Study Completion Date2026-06

Terms related to this study

Keywords Provided by Researchers

Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Prodromal Alzheimer's Disease
Amyloid Plaque
Beta-Amyloid
Down syndrome
Vaccine
Immunogenicity

Additional Relevant MeSH Terms

Alzheimer's Disease
Prodromal Alzheimer's Disease
Amyloid Plaque
Beta-Amyloid
Alzheimer's Disease in Down Syndrome