- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04373616
A Study of ACI-24 in Adults With Down Syndrome
October 14, 2021 updated by: AC Immune SA
A Phase 2 Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability and Target Engagement of ACI-24 in Adults With Down Syndrome
This study is a prospective multicenter, placebo-controlled, double-blind, randomized study to assess the effect of one dose ACI-24 versus placebo over a 74-week treatment period and 26-week safety follow-up period.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
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.
Eligibility Criteria
Ages Eligible for Study
40 years to 50 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21.
- Age ≥ 40 and ≤ 50 years at screening.
- Elevated brain Aβ as evidenced by composite SUVR ≥ 1.25 on florbetaben PET scan assessed by central reading.
- Subjects, their legal representatives (if applicable) and/or their study partners in the opinion of the investigator, are able to understand and to provide written informed consent before starting any study-related activities.
- In the opinion of the investigator, subjects, their legal representatives (if applicable) and/or their study partners are able to fully participate in the study, be sufficiently proficient in the official languages(s) of the country they are living in, and be capable of reliably completing study assessments.
- 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 with the subject and who is able to provide reliable answers to questions related to the subject, according to the study investigator.
- Subjects in preclinical stage of AD or with mild cognitive impairment due to AD.
Exclusion Criteria:
- Clinical diagnosis of AD dementia in DS as per International Classification of Diseases 10 (ICD-10).
- DSQIID > 20.
- Intelligence quotient score ≤ 40 (KBIT-2).
- Diagnosis of autism spectrum disorder or any other unstable/uncontrolled psychiatric or neurologic illness other than DS.
- Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study vaccine (eg, severe and 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.
- Subjects considered to be unable to complete any study exams and assessments (eg, because of significant hearing or visual impairments or other disabilities), according to the investigator, and potentially affecting study compliance.
- 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.
- History of meningitis or meningoencephalitis.
- History of moderate or severe traumatic brain injury.
- History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in-situ, in-situ prostate cancer, or in-situ breast cancer which have been fully removed and are considered cured.
- History of inflammatory neurological disorders.
- History of autoimmune disease with potential for central nervous system involvement.
- Severe infections or a major surgical operation within 3 months before screening.
- History of chronic or recurrent infections judged to be clinically significant by the investigator and would potentially hamper the evaluation of efficacy and safety assessments.
- History or presence of immunological or inflammatory conditions judged to be clinically significant by the investigator.
- History of severe allergic reaction (eg, anaphylaxis) including, but not limited to, severe allergic reaction to previous vaccines, foods, and/or medications.
- Clinically significant abnormal vital signs including sustained sitting blood pressure greater than 160/90 mm Hg.
- Subjects who have donated blood or blood products in the 30 days before screening or who plan to donate blood while participating in the study or within 4 weeks after completion of the study.
- Subjects with diabetes mellitus with hemoglobin A1c (HbA1c) levels of ≥ 8.0%.
- Any contraindication for lumbar puncture for those subjects consenting to the optional lumbar puncture.
- MRI scan at screening showing a single area of cerebral vasogenic edema, superficial siderosis, or evidence of a previous macrohemorrhage 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.
- In the opinion of the site investigator, 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) test at screening.
- Subjects with clinical or laboratory evidence of active Hepatitis B or C at screening.
- Subjects with positive syphilis serology consistent with active syphilis at screening.
- Clinically significant arrhythmias or other abnormalities on ECG at screening (minor abnormalities documented as clinically insignificant by the investigator are allowed).
- Any vaccine received within the 2 weeks before screening, including influenza vaccine.
- Subjects with treated hypothyroidism not on a stable dose of replacement medication for at least 3 months before screening and having clinically significant abnormal serum T4 and/or thyroid-stimulating hormone at screening.
- Subjects who have been receiving any experimental drug with a washout less than 30 days or less than 5 half-lives of the drug, whichever is longer.
- Subjects being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower.
- Use of antidepressants (other than selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors at stable dose); antipsychotics (typical or atypical); 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 assessments, the safety, and the efficacy of the study vaccine according to the site investigator and the site monitor.
- Current use of anticholinergic agents for bladder dysfunction (eg, oxybutynin, tolterodine, darifenacin, solifenacin, trospium, or fesoterodine) or subjects who have received such treatments within a time period corresponding to 5 half-lives of the respective agent before screening.
- Chronic use of opioid analgesics. However, limited treatment duration for acute conditions until 24 hours before cognitive assessment is allowed.
- Current use of antihistaminic agents, especially of first generation. Limited use of second-generation antihistaminics for acute conditions is allowed if not anticipated to influence the cognitive assessments, according to the investigator.
- 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.
- Previous treatment with ACI-24 or any other passive or active immunotherapy against AD and/or for neurological disorders (passive immunization within the 6 months before screening, active immunization at any time point) unless there is firm evidence that the subject was treated with placebo only, and the placebo formulation is not expected to induce any specific immune response.
- Use of acetylcholinesterase inhibitors or use of glutamatergic drugs (eg, memantine, topiramate, lamotrigine) if not on stable dose for at least 2 months before screening.
- Concomitant participation in any other clinical study using an investigational drug.
- Female subjects who are pregnant as confirmed by serum testing at screening or who are planning to become pregnant or lactating.
- Female or male subjects not using a reliable method of contraception during the treatment period and for 26 weeks (6 months) after the last administration of study vaccine.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
injections
|
Experimental: ACI-24
|
injections
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 up to week 100
|
from screening up to week 100
|
|
Mean change from baseline in systolic and diastolic blood pressure (mmHg)
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Mean change from baseline in heart rate (bpm)
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Mean change from baseline in body temperature (degree Celsius)
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Number of participants reporting suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Number of participants with abnormal MRI results
Time Frame: from baseline up to week 100
|
Occurrence of Amyloid-related imaging abnormalities (ARIA)
|
from baseline up to week 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline of composite standardized uptake value ratio (SUVR) assessed by amyloid PET imaging using florbetaben
Time Frame: from baseline up to week 76
|
from baseline up to week 76
|
|
Change from baseline in anti-Aβ antibody titers in blood
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Change from baseline of amyloid-related biomarkers (Aβ1-40, Aβ1-42), total tau, phosphorylated tau and NfL in blood/CSF (in pg/ml) (CSF is optional)
Time Frame: from baseline up to week 100
|
from baseline up to week 100
|
|
Change from baseline of brain tau load assessed by tau PET imaging
Time Frame: from screening up to week 74
|
from screening up to week 74
|
|
Change from baseline of cognitive performance using Cambridge Neuropsychological Test Automated Battery - Paired Associates Learning [CANTAB-PAL]
Time Frame: from baseline up to week 100
|
Score is a z-score ranging from -7.5 to 0. A higher score (eg., 0) indicates a better outcome.
|
from baseline up to week 100
|
Change from baseline of cognitive performance using Cambridge Cognitive Examination - Down Syndrome [CAMCOG-DS]
Time Frame: from baseline up to week 100
|
The total score ranges from 0 to 107.
A higher score indicates a better outcome.
|
from baseline up to week 100
|
Change from baseline in adaptive behavior (Vineland Adaptive Behavior Scale)
Time Frame: from baseline up to week 100
|
The composite score ranges from 20 to 140.
A higher score indicates a better outcome.
|
from baseline up to week 100
|
Change from baseline in Clinical Global Impression of Change (CGIC)
Time Frame: from baseline up to week 100
|
The score ranges from 1 to 7. A higher score indicates a worse outcome.
|
from baseline up to week 100
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Michael S. Rafii, MD, PhD, Alzheimer's Therapeutic Research Institute USC Keck School of Medicine of the University of Southern California, San Diego, CA, 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 Major Dates
Study Start (Anticipated)
October 1, 2021
Primary Completion (Anticipated)
April 1, 2024
Study Completion (Anticipated)
October 1, 2024
Study Registration Dates
First Submitted
April 27, 2020
First Submitted That Met QC Criteria
May 1, 2020
First Posted (Actual)
May 4, 2020
Study Record Updates
Last Update Posted (Actual)
October 22, 2021
Last Update Submitted That Met QC Criteria
October 14, 2021
Last Verified
October 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ACI-24-DS-1902
- 2020-000634-18 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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